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Journal of the American Society of... Dec 2022The kidneys critically contribute to body homeostasis under the control of the autonomic nerves, which enter the kidney along the renal vasculature. Although the renal...
BACKGROUND
The kidneys critically contribute to body homeostasis under the control of the autonomic nerves, which enter the kidney along the renal vasculature. Although the renal sympathetic and sensory nerves have long been confirmed, no significant anatomic evidence exists for renal parasympathetic innervation.
METHODS
We identified cholinergic nerve varicosities associated with the renal vasculature and pelvis using various anatomic research methods, including a genetically modified mouse model and immunostaining. Single-cell RNA sequencing (scRNA-Seq) was used to analyze the expression of in the renal artery and its segmental branches. To assess the origins of parasympathetic projecting nerves of the kidney, we performed retrograde tracing using recombinant adeno-associated virus (AAV) and pseudorabies virus (PRV), followed by imaging of whole brains, spinal cords, and ganglia.
RESULTS
We found that cholinergic axons supply the main renal artery, segmental renal artery, and renal pelvis. On the renal artery, the newly discovered cholinergic nerve fibers are separated not only from the sympathetic nerves but also from the sensory nerves. We also found cholinergic ganglion cells within the renal nerve plexus. Moreover, the scRNA-Seq analysis suggested that acetylcholine receptors (AChRs) are expressed in the renal artery and its segmental branches. In addition, retrograde tracing suggested vagus afferents conduct the renal sensory pathway to the nucleus of the solitary tract (NTS), and vagus efferents project to the kidney.
CONCLUSIONS
Cholinergic nerves supply renal vasculature and renal pelvis, and a vagal brain-kidney axis is involved in renal innervation.
Topics: Mice; Animals; Sympathetic Nervous System; Kidney; Spinal Cord; Pelvis; Cholinergic Agents
PubMed: 36253054
DOI: 10.1681/ASN.2021111518 -
Anatomical Record (Hoboken, N.J. : 2007) Sep 2021The distribution of cholinergic cell bodies and fibers was examined in the mesencephalon and isthmus of Gekko gecko. Distinct groups with prominent labeled cells were... (Review)
Review
The distribution of cholinergic cell bodies and fibers was examined in the mesencephalon and isthmus of Gekko gecko. Distinct groups with prominent labeled cells were observed in the cranial nerve motor nuclei and isthmic nuclei, and weak labeled cell bodies and fibers were observed in the mesencephalic nucleus of the trigeminal nerve and the central nucleus of the torus semicircularis. After discussing the topological relationships within the tectum and isthmus, we unify the nomenclature of the caudal deep mesencephalic nucleus in lizards and the rostral magnocellular nucleus isthmi in turtles that is similar in terms of the preisthmic position, nontopographic connections with the tectum, and the same midbrain origin to the magnocellular preisthmic nucleus in birds, and may be homologous to the superficial cuneiform nucleus in mammals. None of them belong to the cholinergic nucleus isthmi, as the latter has isthmus origin and topographic reciprocal connections with the tectum. We also discuss the origin and intrinsic function of the inner longitudinal tract of the thick ChAT-ir fibers that course through the mesencephalon and diencephalon. We review the subdivisions of the mesencephalon and isthmus of Gekko gecko as revealed by ChAT immunohistochemistry, as well as the limits of the diencephalo-mesencephalic, mesencephalic-isthmo, and isthmo-rhombocephalic by the ChAT-ir cell- and fiber-poor distribution, and discuss the caudal limit of the isthmus. Our research on the subdivisions of the mesencephalon and isthmus in G. gecko as revealed by ChAT immunohistochemistry will serve as the neuroanatomical basis for subsequent relevant studies of Gekko gecko.
Topics: Animals; Choline O-Acetyltransferase; Cholinergic Agents; Immunohistochemistry; Lizards; Mesencephalon
PubMed: 33554451
DOI: 10.1002/ar.24595 -
The International Journal of... May 2021The production and circuit integration of new neurons is one of the defining features of the adult mammalian hippocampus. A wealth of evidence has established that adult... (Review)
Review
The production and circuit integration of new neurons is one of the defining features of the adult mammalian hippocampus. A wealth of evidence has established that adult hippocampal neurogenesis is exquisitely sensitive to neuronal activity-mediated regulation. How these signals are interpreted and contribute to neurogenesis and hippocampal functions has been a subject of immense interest. In particular, neurotransmitters, in addition to their synaptic roles, have been shown to offer important trophic support. Amongst these, acetylcholine, which has a prominent role in cognition, has been implicated in regulating neurogenesis. In this review, we appraise the evidence linking the contribution of cholinergic signalling to the regulation of adult hippocampal neurogenesis and hippocampus-dependent functions. We discuss open questions that need to be addressed to gain a deeper mechanistic understanding of the role and translational potential of acetylcholine and its receptors in regulating this form of cellular neuroplasticity.
Topics: Adult; Animals; Cholinergic Agents; Cognition; Hippocampus; Humans; Neurogenesis; Neuronal Plasticity; Neurons
PubMed: 33727042
DOI: 10.1016/j.biocel.2021.105969 -
Neuroscience Bulletin Apr 2023Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder...
Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
Topics: Rats; Mice; Animals; Rats, Sprague-Dawley; Depressive Disorder, Major; Basal Forebrain; Depression; Hippocampus; Cholinergic Agents
PubMed: 36342657
DOI: 10.1007/s12264-022-00962-2 -
International Journal of Molecular... May 2021All nervous system pathologies (e.g., neurodegenerative/demyelinating diseases and brain tumours) develop neuroinflammation, a beneficial process during pathological... (Review)
Review
All nervous system pathologies (e.g., neurodegenerative/demyelinating diseases and brain tumours) develop neuroinflammation, a beneficial process during pathological events, aimed at removing damaged cells, toxic agents, and/or pathogens. Unfortunately, excessive inflammation frequently occurs during nervous system disorders, becoming a detrimental event capable of enhancing neurons and myelinating glial cell impairment, rather than improving their survival and activity. Consequently, targeting the neuroinflammation could be relevant for reducing brain injury and rescuing neuronal and glial cell functions. Several studies have highlighted the role of acetylcholine and its receptors in the regulation of central and peripheral inflammation. In particular, α7 nicotinic receptor has been described as one of the main regulators of the "brain cholinergic anti-inflammatory pathway". Its expression in astrocytes and microglial cells and the ability to modulate anti-inflammatory cytokines make this receptor a new interesting therapeutic target for neuroinflammation regulation. In this review, we summarize the distribution and physiological functions of the α7 nicotinic receptor in glial cells (astrocytes and microglia) and its role in the modulation of neuroinflammation. Moreover, we explore how its altered expression and function contribute to the development of different neurological pathologies and exacerbate neuroinflammatory processes.
Topics: Animals; Brain; Cholinergic Agents; Humans; Inflammation; Neuroglia; Signal Transduction; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 34066354
DOI: 10.3390/ijms22094912 -
International Journal of Molecular... Apr 2022Organophosphorus pesticides (OPs) are widespread insecticides used for pest control in agricultural activities and the control of the vectors of human and animal... (Review)
Review
Organophosphorus pesticides (OPs) are widespread insecticides used for pest control in agricultural activities and the control of the vectors of human and animal diseases. However, OPs' neurotoxic mechanism involves cholinergic components, which, beyond being involved in the transmission of neuronal signals, also influence the activity of cytokines and other pro-inflammatory molecules; thus, acute and chronic exposure to OPs may be related to the development of chronic degenerative pathologies and other inflammatory diseases. The present article reviews and discusses the experimental evidence linking inflammatory process with OP-induced cholinergic dysregulation, emphasizing the molecular mechanisms related to the role of cytokines and cellular alterations in humans and other animal models, and possible therapeutic targets to inhibit inflammation.
Topics: Animals; Cholinergic Agents; Cytokines; Inflammation; Organophosphorus Compounds; Pesticides
PubMed: 35562914
DOI: 10.3390/ijms23094523 -
Cell Reports Oct 2022Cholinergic interneurons (CINs) are essential elements of striatal circuits and functions. Although acetylcholine signaling via muscarinic receptors (mAChRs) has been...
Cholinergic interneurons (CINs) are essential elements of striatal circuits and functions. Although acetylcholine signaling via muscarinic receptors (mAChRs) has been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on striatal GABAergic interneurons (GINs) are equally critical. One example is that CIN stimulation induces large disynaptic inhibition of striatal projection neurons (SPNs) mediated by nAChR activation of GINs. Although these circuits are ideally positioned to modulate striatal output, the neurons involved are not definitively identified because of an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs modulate four GINs populations via an intricate mechanism involving co-activation of presynaptic and postsynaptic mAChRs and nAChRs. Using optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.
Topics: Acetylcholine; Tyrosine 3-Monooxygenase; Corpus Striatum; Interneurons; Cholinergic Agents; Receptors, Muscarinic; Receptors, Nicotinic; Cholinergic Neurons
PubMed: 36288709
DOI: 10.1016/j.celrep.2022.111531 -
Journal of Neurochemistry Sep 2021Advances in understanding the regulatory functions of the nervous system have revealed neural cholinergic signaling as a key regulator of cytokine responses and... (Review)
Review
Advances in understanding the regulatory functions of the nervous system have revealed neural cholinergic signaling as a key regulator of cytokine responses and inflammation. Cholinergic drugs, including the centrally acting acetylcholinesterase inhibitor, galantamine, which are in clinical use for the treatment of Alzheimer's disease and other neurodegenerative and neuropsychiatric disorders, have been rediscovered as anti-inflammatory agents. Here, we provide a timely update on this active research and clinical developments. We summarize the involvement of cholinergic mechanisms and inflammation in the pathobiology of Alzheimer's disease, Parkinson's disease, and schizophrenia, and the effectiveness of galantamine treatment. We also highlight recent findings demonstrating the effects of galantamine in preclinical and clinical settings of numerous conditions and diseases across the lifespan that are characterized by immunological, neurological, and metabolic dysfunction.
Topics: Acetylcholinesterase; Animals; Anti-Inflammatory Agents; Brain; Cholinergic Agents; Cholinesterase Inhibitors; Galantamine; Humans; Longevity; Mental Disorders; Neurodegenerative Diseases
PubMed: 33219523
DOI: 10.1111/jnc.15243 -
Neuroscience Feb 2021Long-term changes in synaptic transmission between neurons in the brain are considered the cellular basis of learning and memory. Over the last few decades, many studies... (Review)
Review
Long-term changes in synaptic transmission between neurons in the brain are considered the cellular basis of learning and memory. Over the last few decades, many studies have revealed that the precise order and timing of activity between pre- and post-synaptic cells ("spike-timing-dependent plasticity; STDP") is crucial for the sign and magnitude of long-term changes at many central synapses. Acetylcholine (ACh) via the recruitment of diverse muscarinic receptors is known to influence STDP in a variety of ways, enabling flexibility and adaptability in brain network activity during complex behaviors. In this review, we will summarize and discuss different mechanistic aspects of muscarinic modulation of timing-dependent plasticity at both excitatory and inhibitory synapses in the hippocampus to shape learning and memory.
Topics: Action Potentials; Cholinergic Agents; Hippocampus; Neuronal Plasticity; Synapses; Synaptic Transmission
PubMed: 32828940
DOI: 10.1016/j.neuroscience.2020.08.015 -
American Journal of Physiology. Heart... Nov 2022Cognitive decline is linked to decreased cerebral blood flow, particularly in women after menopause. Impaired cerebrovascular function precedes the onset of dementia,...
Cognitive decline is linked to decreased cerebral blood flow, particularly in women after menopause. Impaired cerebrovascular function precedes the onset of dementia, possibly because of reduced functional dilation in parenchymal arterioles. These vessels are bottlenecks of the cerebral microcirculation, and dysfunction can limit functional hyperemia in the brain. Large-conductance Ca-activated K channels (BK) are the final effectors of several pathways responsible for functional hyperemia, and their expression is modulated by estrogen. However, it remains unknown whether BK function is altered in cerebral parenchymal arterioles after menopause. Using a chemically induced model of menopause, the 4-vinylcyclohexene diepoxide (VCD) model, which depletes follicles while maintaining intact ovaries, we hypothesized that menopause would be associated with reduced functional vasodilatory responses in cerebral parenchymal arterioles of wild-type mice via reduced BK function. Using pressure myography of isolated parenchymal arterioles, we observed that menopause (Meno) induced a significant increase in spontaneous myogenic tone. Endothelial function, assessed as nitric oxide production and dilation after cholinergic stimulation or endothelium-dependent hyperpolarization pathways, was unaffected by Meno. BK function was significantly impaired in Meno compared with control, without changes in voltage-gated K channel activity. Cerebral functional hyperemia, measured by laser-speckle contrast imaging during whisker stimulation, was significantly blunted in Meno mice, without detectable changes in basal perfusion. However, behavioral testing identified no change in cognition. These findings suggest that menopause induces cerebral microvascular and neurovascular deficits. Cerebral parenchymal arterioles from menopause mice showed increased myogenic tone. We identified an impairment in smooth muscle cell BK channel activity, without a reduction in endothelium-dependent dilation or nitric oxide production. Microvascular dysfunction was associated with a reduction in neurovascular responses after somatosensory stimulation. Despite the neurovascular impairment, cognitive abilities were maintained in menopausal mice.
Topics: Animals; Arterioles; Cerebrovascular Disorders; Cholinergic Agents; Estrogens; Female; Hyperemia; Menopause; Mice; Nitric Oxide
PubMed: 36149767
DOI: 10.1152/ajpheart.00276.2022