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Acupuncture for neurogenesis in experimental ischemic stroke: a systematic review and meta-analysis.Scientific Reports Jan 2016Acupuncture has been used for patients with stroke and post-stroke rehabilitation for thousands of years. Previous studies reported that acupuncture enhanced stroke... (Meta-Analysis)
Meta-Analysis Review
Acupuncture has been used for patients with stroke and post-stroke rehabilitation for thousands of years. Previous studies reported that acupuncture enhanced stroke recovery through neurogenesis. Hence, we conducted a systematic review and meta-analysis for preclinical studies to assess the current evidence for acupuncture effect on neurogenesis in treating ischaemic stroke. Studies were obtained from six databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, and Chinese Biomedical Literature Database, Ultimately, 34 studies containing 1617 animals were identified. Neurogenesis markers of Brdu, Nestin, PSA-NCAM, NeuN and GFAP were selected as major outcomes. The pooled results of 15 studies marked with Brdu showed significant effects of acupuncture for improving proliferation when compared with control groups (P < 0.01); 13 studies marked with Nestin showed significant effects of acupuncture for increasing proliferation when compared with control groups (P < 0.01); 4 studies marked with PSA-NCAM showed significant effects of acupuncture for enhancing migration when compared with control groups (P < 0.01); 4 studies marked with NeuN showed significant effects of acupuncture for stimulating differentiation when compared with control groups (P < 0.01). The findings suggest that acupuncture is a prospective therapy targeting neurogenesis for ischemic stroke.
Topics: Acupuncture; Acupuncture Therapy; Animals; Biomarkers; Brain; Cell Differentiation; Cell Movement; Cell Proliferation; Disease Models, Animal; Humans; Neurogenesis; Publication Bias; Stroke; Treatment Outcome
PubMed: 26786869
DOI: 10.1038/srep19521 -
Frontiers in Psychiatry 2021Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce...
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies ( = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.
PubMed: 34566723
DOI: 10.3389/fpsyt.2021.724606 -
Pediatric Research Jan 2020Neonatal intensive care practices have resulted in marked improvements in the survival of premature infants; however, they remain at significant risk for adverse...
BACKGROUND
Neonatal intensive care practices have resulted in marked improvements in the survival of premature infants; however, they remain at significant risk for adverse neurodevelopmental outcomes. The impact of current nutritional practices on brain development following early extra-uterine exposure in premature infants is not well known.
METHODS
We performed a systematic review to investigate nutritional effects on postnatal brain development in healthy term and prematurely born infants utilizing advanced magnetic resonance imaging tools.
RESULTS
Systematic screen yielded 595 studies for appraisal. Of these, 22 total studies were selected for inclusion in the review, with findings summarized in a qualitative, descriptive fashion.
CONCLUSION
Fat and energy intake are associated with improved brain volume and development in premature infants. While breast milk intake and long-chain polyunsaturated fatty acid supplementation has been proven beneficial in term infants, the impact in preterm infants is less well understood.
Topics: Age Factors; Bottle Feeding; Brain; Breast Feeding; Child Development; Gestational Age; Humans; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Magnetic Resonance Imaging; Neurogenesis; Nutritional Status; Premature Birth
PubMed: 31349359
DOI: 10.1038/s41390-019-0508-3 -
Nutrients May 2022Vitamin E deficiency (VED) is associated with clinical repercussions in preterm newborns (PTN), but low levels are also found in full-term newborns (TN). As this... (Review)
Review
Vitamin E deficiency (VED) is associated with clinical repercussions in preterm newborns (PTN), but low levels are also found in full-term newborns (TN). As this inadequacy can compromise neurogenesis in childhood, studies are needed to assess whether there is a difference in vitamin E status among newborns according to gestational age to provide support for neonatal monitoring protocols. This systematic review presents a synthesis of the available information on the vitamin E status among PTN and TN. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Observational studies that evaluated alpha-tocopherol levels were searched in the databases reported in the protocol registered in PROSPERO (CRD42021165152). The Newcastle-Ottawa Scale was used to assess the methodological quality. Overall, 1809 articles were retrieved; 10 were included in the systematic review. In the PTN, the alpha-tocopherol levels ranged from 3.9 to 8.5 mmol/L, while in TN, they were 4.9 to 14.9 mmol/L, and VED ranged from 19% to 100% in newborns. Despite substantial heterogeneity in research methodology and VED classification, the results suggest that the alpha-tocopherol levels among preterm and full-term newborns is below the recommended levels. Our findings demonstrate that further investigations are needed to standardize this classification and to monitor vitamin E status in birth and postnatal with adequate bias control.
Topics: Gestational Age; Humans; Infant; Infant, Newborn; Vitamin E; Vitamin E Deficiency; alpha-Tocopherol
PubMed: 35684057
DOI: 10.3390/nu14112257 -
Molecular Psychiatry Oct 2023Adolescence represents a critical period for brain and behavioural health and characterised by the onset of mood, psychotic and anxiety disorders. In rodents,...
Adolescence represents a critical period for brain and behavioural health and characterised by the onset of mood, psychotic and anxiety disorders. In rodents, neurogenesis is very active during adolescence, when is particularly vulnerable to stress. Whether stress-related neurogenesis changes influence adolescence onset of psychiatric symptoms remains largely unknown. A systematic review was conducted on studies investigating changes in hippocampal neurogenesis and neuroplasticity, hippocampal-dependent cognitive functions, and behaviour, occurring after adolescence stress exposure in mice both acutely (at post-natal days 21-65) and in adulthood. A total of 37 studies were identified in the literature. Seven studies showed reduced hippocampal cell proliferation, and out of those two reported increased depressive-like behaviours, in adolescent rodents exposed to stress. Three studies reported a reduction in the number of new-born neurons, which however were not associated with changes in cognition or behaviour. Sixteen studies showed acutely reduced hippocampal neuroplasticity, including pre- and post-synaptic plasticity markers, dendritic spine length and density, and long-term potentiation after stress exposure. Cognitive impairments and depressive-like behaviours were reported by 11 of the 16 studies. Among studies who looked at adolescence stress exposure effects into adulthood, seven showed that the negative effects of stress observed during adolescence on either cell proliferation or hippocampal neuroplasticity, cognitive deficits and depressive-like behaviour, had variable impact in adulthood. Treating adolescent mice with antidepressants, glutamate receptor inhibitors, glucocorticoid antagonists, or healthy diet enriched in omega-3 fatty acids and vitamin A, prevented or reversed those detrimental changes. Future research should investigate the translational value of these preclinical findings. Developing novel tools for measuring hippocampal neurogenesis in live humans, would allow assessing neurogenic changes following stress exposure, investigating relationships with psychiatric symptom onset, and identifying effects of therapeutic interventions.
Topics: Animals; Mice; Brain; Cognition; Hippocampus; Neurogenesis; Rodentia; Stress, Psychological
PubMed: 37612364
DOI: 10.1038/s41380-023-02229-2 -
International Journal of Molecular... Jan 2023Chemokines are known to be immunoregulatory proteins involved not only in lymphocyte chemotaxis to the site of inflammation, but also in neuromodulation, neurogenesis,... (Review)
Review
Chemokines are known to be immunoregulatory proteins involved not only in lymphocyte chemotaxis to the site of inflammation, but also in neuromodulation, neurogenesis, and neurotransmission. Multiple lines of evidence suggest a peripheral proinflammatory state and neuroinflammation in at least a third of patients with schizophrenia. Therefore, chemokines can be active players in these processes. In this systematic review, we analyzed the available data on chemokine dysregulation in schizophrenia and the association of chemokines with neuroinflammation. It has been shown that there is a genetic association of chemokine and chemokine receptor gene polymorphisms in schizophrenia. Besides, the most reliable data confirmed by the results of meta-analyses showed an increase in CXCL8/IL-8, CCL2/MCP-1, CCL4/MIP-1β, CCL11/eotaxin-1 in the blood of patients with schizophrenia. An increase in CXCL8 has been found in cerebrospinal fluid, but other chemokines have been less well studied. Increased/decreased expression of genes of chemokine and their receptors have been found in different areas of the brain and peripheral immune cells. The peripheral proinflammatory state may influence the expression of chemokines since their expression is regulated by pro- and anti-inflammatory cytokines. Mouse models have shown an association of schizophrenia with dysregulation of the CX3CL1-CX3CR1 and CXCL12-CXCR4 axes. Altogether, dysregulation in chemokine expression may contribute to neuroinflammation in schizophrenia. In conclusion, this evidence indicates the involvement of chemokines in the neurobiological processes associated with schizophrenia.
Topics: Animals; Mice; Schizophrenia; Neuroinflammatory Diseases; Chemokines; Cytokines; Chemokine CCL2; Chemokine CCL4; Chemotaxis, Leukocyte; Chemokine CCL5
PubMed: 36768537
DOI: 10.3390/ijms24032215 -
Journal of Alzheimer's Disease Reports Apr 2020Nitric oxide/cyclic guanosine monophosphate (cGMP) signaling is compromised in Alzheimer's disease (AD), and phosphodiesterase 5 (PDE5), which degrades cGMP, is... (Review)
Review
Nitric oxide/cyclic guanosine monophosphate (cGMP) signaling is compromised in Alzheimer's disease (AD), and phosphodiesterase 5 (PDE5), which degrades cGMP, is upregulated. Sildenafil inhibits PDE5 and increases cGMP levels. Integrating previous findings, we determine that most doses of sildenafil (especially low doses) likely activate peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) via protein kinase G-mediated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) phosphorylation and/or Sirtuin-1 activation and PGC1α deacetylation. Via PGC1α signaling, low-dose sildenafil likely suppresses β-secretase 1 expression and amyloid-β (Aβ) generation, upregulates antioxidant enzymes, and induces mitochondrial biogenesis. Plus, sildenafil should increase brain perfusion, insulin sensitivity, long-term potentiation, and neurogenesis while suppressing neural apoptosis and inflammation. A systematic review of sildenafil in AD was undertaken. sildenafil protected neural mitochondria from Aβ and advanced glycation end products. In transgenic AD mice, sildenafil was found to rescue deficits in CREB phosphorylation and memory, upregulate brain-derived neurotrophic factor, reduce reactive astrocytes and microglia, decrease interleukin-1β, interleukin-6, and tumor necrosis factor-α, decrease neural apoptosis, increase neurogenesis, and reduce tau hyperphosphorylation. All studies that tested Aβ levels reported significant improvements except the two that used the highest dosage, consistent with the dose-limiting effect of cGMP-induced phosphodiesterase 2 (PDE2) activation and cAMP depletion on PGC1α signaling. In AD patients, a single dose of sildenafil decreased spontaneous neural activity, increased cerebral blood flow, and increased the cerebral metabolic rate of oxygen. A randomized control trial of sildenafil (ideally with a PDE2 inhibitor) in AD patients is warranted.
PubMed: 32467879
DOI: 10.3233/ADR-200166 -
PloS One 2014Few studies that examine the neurogenesis-behaviour relationship formally establish covariation between neurogenesis and behaviour or rule out competing explanations.... (Meta-Analysis)
Meta-Analysis Review
Few studies that examine the neurogenesis-behaviour relationship formally establish covariation between neurogenesis and behaviour or rule out competing explanations. The behavioural relevance of neurogenesis might therefore be overestimated if other mechanisms account for some, or even all, of the experimental effects. A systematic review of the literature was conducted and the data reanalysed using causal mediation analysis, which can estimate the behavioural contribution of new hippocampal neurons separately from other mechanisms that might be operating. Results from eleven eligible individual studies were then combined in a meta-analysis to increase precision (representing data from 215 animals) and showed that neurogenesis made a negligible contribution to behaviour (standarised effect = 0.15; 95% CI = -0.04 to 0.34; p = 0.128); other mechanisms accounted for the majority of experimental effects (standardised effect = 1.06; 95% CI = 0.74 to 1.38; p = 1.7×10-11).
Topics: Affect; Animals; Cognition; Hippocampus; Humans; Memory; Neurogenesis
PubMed: 25426717
DOI: 10.1371/journal.pone.0113855 -
In the pursuit of new social neurons. Neurogenesis and social behavior in mice: A systematic review.Frontiers in Cell and Developmental... 2022Social behaviors have become more relevant to our understanding of the human nervous system because relationships with our peers may require and modulate adult... (Review)
Review
Social behaviors have become more relevant to our understanding of the human nervous system because relationships with our peers may require and modulate adult neurogenesis. Here, we review the pieces of evidence we have to date for the divergence of social behaviors in mice by modulation of adult neurogenesis or if social behaviors and the social environment can drive a change in neurogenic processes. Social recognition and memory are deeply affected by antimitotic drugs and irradiation, while NSC transgenic mice may run with lower levels of social discrimination. Interestingly, social living conditions can create a big impact on neurogenesis. Social isolation and social defeat reduce the number of new neurons, while social dominance and enrichment of the social environment increase their number. These new "social neurons" trigger functional modifications with amazing transgenerational effects. All of these suggest that we are facing two bidirectional intertwined variables, and the great challenge now is to understand the cellular and genetic mechanisms that allow this relationship to be used therapeutically.
PubMed: 36407114
DOI: 10.3389/fcell.2022.1011657 -
International Journal of Molecular... Dec 2022Growing evidence suggests a possible involvement of the intestinal microbiota in generating new neurons, but a detailed breakdown of the microbiota composition is... (Review)
Review
Growing evidence suggests a possible involvement of the intestinal microbiota in generating new neurons, but a detailed breakdown of the microbiota composition is lacking. In this report, we systematically reviewed preclinical rodent reports addressing the connection between the composition of the intestinal microbiota and neurogenesis and neurogenesis-affecting neurotrophins in the hippocampus. Various changes in bacterial composition from low taxonomic resolution at the phylum level to high taxonomic resolution at the species level were identified. As for neurogenesis, studies predominantly used doublecortin (DCX) as a marker of newly formed neurons or bromodeoxyuridine (BrdU) as a marker of proliferation. Brain-derived neurotrophic factor (BDNF) was the only neurotrophin found researched in relation to the intestinal microbiota. Phylum Actinobacteria, genus and genus found the strongest positive. In contrast, phylum Firmicutes, phylum Bacteroidetes, and family Enterobacteriaceae, as well as germ-free status, showed the strongest negative correlation towards neurogenesis or BDNF mRNA expression. Age, short-chain fatty acids (SCFA), obesity, and chronic stress were recurring topics in all studies identified. Overall, these findings add to the existing evidence of a connection between microbiota and processes in the brain. To better understand this interaction, further investigation based on analyses of higher taxonomic resolution and clinical studies would be a gain to the matter.
Topics: Brain-Derived Neurotrophic Factor; Gastrointestinal Microbiome; Neurogenesis; Hippocampus; Brain; Bacteria
PubMed: 36555576
DOI: 10.3390/ijms232415934