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CNS Neuroscience & Therapeutics Feb 2024Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and... (Review)
Review
BACKGROUND AND OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS.
METHODS
A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS.
RESULTS
A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory.
CONCLUSIONS
The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.
Topics: Humans; Diffusion Tensor Imaging; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Frontotemporal Dementia; Magnetic Resonance Imaging; Hippocampus; Biomarkers; Neuropsychological Tests; Atrophy
PubMed: 38334254
DOI: 10.1111/cns.14578 -
Frontiers in Physiology 2023Studies have shown that exercise increases angiogenesis and perfusion in the hippocampus, activates neurogenesis in the dentate gyrus and increases synaptic plasticity,...
Studies have shown that exercise increases angiogenesis and perfusion in the hippocampus, activates neurogenesis in the dentate gyrus and increases synaptic plasticity, as well as increases the complexity and number of dendritic spines, all of which promote memory function and protect against cognitive decline. Flavonoids are gaining attention as antioxidants in health promotion due to their rich phenolic content, particularly for their modulating role in the treatment of neurodegenerative diseases. Despite this, there has been no comprehensive review of cognitive improvement supplemented with flavonoid and prescribed with exercise or a combination of the two interventions has been conducted. The purpose of this review is to determine whether a combined intervention produces better results when given together than when given separately. Relevant articles assessing the effect of physical exercise, flavonoid or in combination on cognitive related biomarkers and neurobehavioral assessments within the timeline of January 2011 until June 2023 were searched using three databases; PubMed, PROQUEST and SCOPUS. A total of 705 articles were retrieved and screened, resulting in 108 studies which are in line with the objective of the current study were included in the analysis. The selected studies have shown significant desired effect on the chosen biomarkers and neurobehavioral assessments. identifier: [CRD42021271001].
PubMed: 37664425
DOI: 10.3389/fphys.2023.1216948 -
Experimental Neurology Jul 2023Cerebral palsy (CP) is a neurodevelopmental disorder caused by damage to the immature brain. CP is considered the main cause of physical disability in childhood. Studies... (Meta-Analysis)
Meta-Analysis Review
Therapeutic advances for treating memory impairments in perinatal brain injuries with implications for cerebral palsy: a systematic review and meta-analysis of preclinical studies.
Cerebral palsy (CP) is a neurodevelopmental disorder caused by damage to the immature brain. CP is considered the main cause of physical disability in childhood. Studies have shown that memory function and emotional behaviour are significantly impaired in CP. Current thought is that interventions for neuromotor damaged play a prominent role, but neglects the memory acquisition problems that affect the functioning and quality of life of these children. This systematic review aims to map and analyse pre-clinical interventions used to treat memory formation problems resulting from CP. For this, a search was carried out in the Pubmed, Web of Science, Scopus and Lilacs databases. Then, eligibility, extraction date and evaluation of the methodological quality of the studies were determined. 52 studies were included in this review, and 27 were included in a meta-analysis. Assessing memory performance as a primary outcome, and structural and biochemical changes in the hippocampus as a secondary outcome. CP models were reported to be induced by hypoxia-ischemia, oxygen deprivation and liposaccharide (LPS) exposure, resulting in impairments in the formation of short-term and long-term memory in adult life. A reduction in escape latency and dwell time were observed in the target quadrant as well as an increase in the time needed for the rodents to find the platform in the Morris Water Maze (MWM). Brain injuries during the perinatal period are considered an insult that negatively impacts hippocampus maturation and causes impairment in memory formation in adult life. Some studies reported that regions of the hippocampus such as the dentate gyrus and cornu ammonis 1 were impaired in CP, noting an increase in oxidative stress enzymes and pro-inflammatory cytokines, associated with a reduction in BDNF and neurogenesis levels. These were reported to cause a reduction in the number of neurons and the volume of the hippocampus, in addition to an increase in astrogliosis and apoptosis of neurons and difficulties in forming new memories similar to those that occur in children with CP. Interventions that reduced neuroinflammation and the presence of free radicals were highlighted as a therapy for the memory disturbance present in CP. Preclinical studies registered treatments with oxygen interventions, resveratrol and erythropoietin, which were able to reduce the damage to the hippocampus and promote improvements in memory and behaviour. In the meta-analysis of selected studies, we observed favorable results, through effect size, for the use of oxygen interventions (SDM -6.83 95% CI [-7.91, -5.75], Z = 12.38, p = 0.03; I2 = 71%), erythropoietin (SDM -3.16 95% CI [-4.27, -2.05], Z = 5.58, p = 0.002; I2 = 82%) and resveratrol (SDM -2.42 95% CI [-3.19, - 1.66], Z = 6.21, p = 0.01; I2 = 77%), stimulating plastic responses in the hippocampus and facilitating the memory formation, with these presenting positive effects in general (SDM -2.84 95% CI [-3.10, -2.59], Z = 22.00; p < 0.00001; I2 = 92.9%). These studies demonstrate possible avenues of intervention for memory alterations in experimental models of early brain injuries, highlighting promising interventions that can facilitate the maturation of the hippocampus and memory formation and, consequently, minimize functional problems that arise during development.
Topics: Humans; Cerebral Palsy; Quality of Life; Resveratrol; Hippocampus; Memory Disorders; Brain Injuries; Erythropoietin
PubMed: 37068620
DOI: 10.1016/j.expneurol.2023.114411 -
Journal of Psychiatry & Neuroscience :... 2023Hippocampal disturbances are important in the pathophysiology of both schizophrenia and major depressive disorder (MDD). Imaging studies have shown selective volume... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hippocampal disturbances are important in the pathophysiology of both schizophrenia and major depressive disorder (MDD). Imaging studies have shown selective volume deficits across hippocampal subfields in both disorders. We aimed to investigate whether these volumetric alterations in hippocampal subfields are shared or divergent across disorders.
METHODS
We searched PubMed and Embase from database inception to May 8, 2021. We identified MRI studies in patients with schizophrenia, MDD or both, in which hippocampal subfield volumes were measured. We excluded nonoriginal, animal or postmortem studies, and studies that used other imaging modalities or overlapping data. We conducted a network meta-analysis to estimate and contrast alterations in subfield volumes in the 2 disorders.
RESULTS
We identified 45 studies that met the initial criteria for systematic review, of which 15 were eligible for network metaanalysis. Compared to healthy controls, patients with schizophrenia had reduced volumes in the bilateral cornu ammonis (CA) 1, granule cell layer of the dentate gyrus, subiculum, parasubiculum, molecular layer, hippocampal tail and hippocampus-amygdala transition area (HATA); in the left CA4 and presubiculum; and in the right fimbria. Patients with MDD had decreased volumes in the left CA3 and CA4 and increased volumes in the right HATA compared to healthy controls. The bilateral parasubiculum and right HATA were smaller in patients with schizophrenia than in patients with MDD.
LIMITATIONS
We did not investigate medication effects because of limited information. Study heterogeneity was noteworthy in direct comparisons between patients with MDD and healthy controls.
CONCLUSION
The volumes of multiple hippocampal subfields are selectively altered in patients with schizophrenia and MDD, with overlap and differentiation in subfield alterations across disorders. Rigorous head-to-head studies are needed to validate our findings.
Topics: Humans; Depressive Disorder, Major; Network Meta-Analysis; Schizophrenia; Hippocampus; Magnetic Resonance Imaging; Organ Size
PubMed: 36750240
DOI: 10.1503/jpn.220086 -
Journal of Neurology May 2023To evaluate the difference of tau burden between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs) or other neurodegenerative diseases using... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the difference of tau burden between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs) or other neurodegenerative diseases using tau-positron emission tomography (PET) imaging.
METHODS
A systematic search on PubMed, Embase, and Web of Science databases was performed for tau-PET studies in PSP patients, up to April 1, 2022. Standardized mean differences (SMDs) of tau tracer uptake were calculated using random-effects models. Subgroup analysis based on the type of tau tracers, meta-regression, and sensitivity analysis were conducted.
RESULTS
Twenty-seven studies comprising 553 PSP, 626 HCs, and 406 other neurodegenerative diseases were included. Compared with HCs, PSP patients showed elevated tau binding in basal ganglia, midbrain, dentate nucleus, cerebellar white matter, and frontal lobe with decreasing SMD (SMD: 0.390-1.698). Compared with Parkinson's disease patients, increased tau binding was identified in the midbrain, basal ganglia, dentate nucleus, and frontal and parietal lobe in PSP patients with decreasing SMD (SMD: 0.503-1.853). PSP patients showed higher tau binding in the subthalamic nucleus (SMD = 1.351) and globus pallidus (SMD = 1.000), and lower binding in the cortex and parahippocampal gyrus than Alzheimer's disease patients (SMD: - 2.976 to - 1.018). PSP patients showed higher midbrain tau binding than multiple system atrophy patients (SMD = 1.269).
CONCLUSION
Tau PET imaging indicates different topography of tau deposition between PSP patients and HCs or other neurodegenerative disorders. The affinity and selectivity of tracers for 4R-tau and the off-target binding of tracers should be considered when interpreting the results.
Topics: Humans; Supranuclear Palsy, Progressive; tau Proteins; Basal Ganglia; Parkinson Disease; Positron-Emission Tomography
PubMed: 36633672
DOI: 10.1007/s00415-022-11556-3 -
Human Brain Mapping Apr 2023Specific subfields within the hippocampus have shown vulnerability to chronic stress, highlighting the importance of looking regionally within the hippocampus to...
Specific subfields within the hippocampus have shown vulnerability to chronic stress, highlighting the importance of looking regionally within the hippocampus to understand the role of psychosocial factors in the development of neurodegenerative diseases. A systematic review on psychosocial factors and hippocampal subfield volumes was performed and showed inconsistent results, highlighting the need for future studies to explore this relationship. The current study aimed to explore the association of psychosocial factors with hippocampal (subfield) volumes, using high-field 7T MRI. Data were from the Memory Depression and Aging (Medea)-7T study, which included 333 participants without dementia. Hippocampal subfields were automatically segmented from T2-weighted images using ASHS software. Generalized linear models accounting for correlated outcomes were used to assess the association between subfields (i.e., entorhinal cortex, subiculum, Cornu Ammonis [CA]1, CA2, CA3, dentate gyrus, and tail) and each psychosocial factor (i.e., depressive symptoms, anxiety symptoms, childhood maltreatment, recent stressful life events, and social support), adjusted for age, sex, and intracranial volume. Neither depression nor anxiety was associated with specific hippocampal (subfield) volumes. A trend for lower total hippocampal volume was found in those reporting childhood maltreatment, and a trend for higher total hippocampal volume was found in those who experienced a recent stressful life event. Among subfields, low social support was associated with lower volume in the CA3 (B = -0.43, 95% CI: -0.72; -0.15). This study suggests possible differential effects among hippocampal (subfield) volumes and psychosocial factors.
Topics: Humans; Organ Size; Hippocampus; CA1 Region, Hippocampal; Aging; Entorhinal Cortex; Magnetic Resonance Imaging
PubMed: 36583397
DOI: 10.1002/hbm.26185 -
Metabolic Brain Disease Jan 2022Evidence on adult mammalian neurogenesis and scarce studies with human brains led to the idea that adult human neurogenesis occurs in the subgranular zone (SGZ) of the... (Review)
Review
Evidence on adult mammalian neurogenesis and scarce studies with human brains led to the idea that adult human neurogenesis occurs in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). However, findings published from 2018 rekindled controversies on adult human SGZ neurogenesis. We systematically reviewed studies published during the first decade of characterization of adult human neurogenesis (1994-2004) - when the two-neurogenic-niche concept in humans was consolidated - and compared with further studies. The synthesis of both periods is that adult human neurogenesis occurs in an intensity ranging from practically zero to a level comparable to adult mammalian neurogenesis in general, which is the prevailing conclusion. Nonetheless, Bernier and colleagues showed in 2000 intriguing indications of adult human neurogenesis in a broad area including the limbic system. Likewise, we later showed evidence that limbic and hypothalamic structures surrounding the circumventricular organs form a continuous zone expressing neurogenesis markers encompassing the SGZ and SVZ. The conclusion is that publications from 2018 on adult human neurogenesis did not bring novel findings on location of neurogenic niches. Rather, we expect that the search of neurogenesis beyond the canonical adult mammalian neurogenic niches will confirm our indications that adult human neurogenesis is orchestrated in a broad brain area. We predict that this approach may, for example, clarify that human hippocampal neurogenesis occurs mostly in the CA1-subiculum zone and that the previously identified human rostral migratory stream arising from the SVZ is indeed the column of the fornix expressing neurogenesis markers.
Topics: Adult; Animals; Brain; Hippocampus; Humans; Lateral Ventricles; Mammals; Neural Stem Cells; Neurogenesis
PubMed: 34739659
DOI: 10.1007/s11011-021-00864-8 -
PloS One 2020Recent results have established that masticatory function plays a role not only in the balance of the stomatognathic system and in the central motor control, but also in...
Altered mastication adversely impacts morpho-functional features of the hippocampus: A systematic review on animal studies in three different experimental conditions involving the masticatory function.
Recent results have established that masticatory function plays a role not only in the balance of the stomatognathic system and in the central motor control, but also in the trophism of the hippocampus and in the cognitive activity. These implications have been shown in clinical studies and in animal researches as well, by means of histological, biochemical and behavioural techniques. This systematic review describes the effects of three forms of experimentally altered mastication, namely soft-diet feeding, molar extraction and bite-raising, on the trophism and function of the hippocampus in animal models. Through a systematic search of PubMed, Embase, Web of Science, Scopus, OpenGray and GrayMatters, 645 articles were identified, 33 full text articles were assessed for eligibility and 28 articles were included in the review process. The comprehensiveness of reporting was evaluated with the ARRIVE guidelines and the risk of bias with the SYRCLE RoB tool. The literature reviewed agrees that a disturbed mastication is significantly associated with a reduced number of hippocampal pyramidal neurons in Cornu Ammonis (CA)1 and CA3, downregulation of Brain Derived Neurotrophic Factor (BDNF), reduced synaptic activity, reduced neurogenesis in the Dentate Gyrus (DG), glial proliferation, and reduced performances in behavioural tests, indicating memory impairment and reduced spatial orientation. Moreover, while the bite-raised condition, characterized by occlusal instability, is known to be a source of stress, soft-diet feeding and molar extractions were not consistently associated with a stress response. More research is needed to clarify this topic. The emerging role of chewing in the preservation of hippocampal trophism, neurogenesis and synaptic activity is worthy of interest and may contribute to the study of neurodegenerative diseases in new and potentially relevant ways.
Topics: Animals; Cognition; Dentate Gyrus; Hippocampus; Humans; Mastication; Memory Disorders; Models, Animal; Neurogenesis; Neurons
PubMed: 32817680
DOI: 10.1371/journal.pone.0237872 -
Alcoholism, Clinical and Experimental... Jun 2020Marijuana and alcohol are both substances that, when used during pregnancy, may have profound effects on the developing fetus. There is evidence to suggest that both...
BACKGROUND
Marijuana and alcohol are both substances that, when used during pregnancy, may have profound effects on the developing fetus. There is evidence to suggest that both drugs have the capacity to affect working memory, one function of the hippocampal formation; however, there is a paucity of data on how perinatal exposure to alcohol or cannabis impacts the process of adult neurogenesis.
METHODS
This systematic review examines immunohistochemical data from adult rat and mouse models that assess perinatal alcohol or perinatal marijuana exposure. A comprehensive list of search terms was designed and used to search 3 separate databases. All results were imported to Mendeley and screened by 2 authors. Consensus was reached on a set of final papers that met the inclusion criteria, and their results were summarized.
RESULTS
Twelve papers were identified as relevant, 10 of which pertained to the effects of perinatal alcohol on the adult hippocampus, and 2 pertained to the effects of perinatal marijuana on the adult hippocampus. Cellular proliferation in the dentate gyrus was not affected in adult rats and mice exposed to alcohol perinatally. In general, perinatal alcohol exposure did not have a significant and reliable effect on the maturation and survival of adult born granule neurons in the dentate gyrus. In contrast, interneuron numbers appear to be reduced in the dentate gyrus of adult rats and mice exposed perinatally to alcohol. Perinatal marijuana exposure was also found to reduce inhibitory interneuron numbers in the dentate gyrus.
CONCLUSIONS
Perinatal alcohol exposure and perinatal marijuana exposure both act on inhibitory interneurons in the hippocampal formation of adult rats. These findings suggest simultaneous perinatal alcohol and marijuana exposure (SAM) may have a dramatic impact on inhibitory processes in the dentate gyrus.
Topics: Alcohol Drinking; Animals; Cannabinoid Receptor Agonists; Central Nervous System Depressants; Dentate Gyrus; Dronabinol; Ethanol; Female; Marijuana Use; Mice; Neurogenesis; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rats
PubMed: 32246781
DOI: 10.1111/acer.14332 -
Pharmacology & Therapeutics Jun 2020The neurogenic hypothesis of depression states that adult hippocampal neurogenesis is disrupted by stress and depression and is recovered by chronic treatments with... (Meta-Analysis)
Meta-Analysis
The neurogenic hypothesis of depression states that adult hippocampal neurogenesis is disrupted by stress and depression and is recovered by chronic treatments with antidepressants. Indeed, chronic antidepressant treatments increased newborn neurons in the adult dentate gyrus in many early studies. However, conflicting findings appeared over time. Thus, our motivation to write this unbiased systematic review and meta-analysis was to answer the following question: can antidepressants reliably promote neurogenesis in adult hippocampus? A meta-analysis was performed on studies in naive rodents. Results indicated that increased neurogenesis is a more nuanced, compound-dependent action of antidepressants than a yes-or-no event. This nuanced notion can lead to a new understanding of the concepts of neurogenic-dependent and neurogenic-independent effects of antidepressants, which would be better described as effects "more-dependent" or "less-dependent" on hippocampal neurogenesis. Further studies are on the way to investigate the strength of the causal relationship between adult hippocampal neurogenesis and behavioural effects of antidepressants.
Topics: Age Factors; Animals; Antidepressive Agents; Behavior, Animal; Depression; Disease Models, Animal; Hippocampus; Mice; Neurogenesis; Rats
PubMed: 32109488
DOI: 10.1016/j.pharmthera.2020.107515