Cholecystokinin (CCK): a neuromodulator with therapeutic potential in Alzheimer’s and Parkinson’s disease

Frontiers in Neuroendocrinology, Год журнала: 2024, Номер 73, С. 101122 - 101122

Опубликована: Фев. 11, 2024

Cholecystokinin (CCK) is a neuropeptide modulating digestion, glucose levels, neurotransmitters and memory. Recent studies suggest that CCK exhibits neuroprotective effects in Alzheimer's disease (AD) Parkinson's (PD). Thus, we review the physiological function therapeutic potential of CCK. The facilitates hippocampal glutamate release gates GABAergic basket cell activity, which improves declarative memory acquisition, but inhibits consolidation. Cortical alters recognition enhances audio-visual processing. By stimulating CCK-1 receptors (CCK-1Rs), sulphated CCK-8 elicits dopamine substantia nigra striatum. In mesolimbic pathway, triggered by terminates reward responses via CCK-2Rs. Importantly, activation nigral CCK-2Rs evoking AMPK activation, expression mitochondrial fusion modulators autophagy. Other benefits include vagus nerve/CCK-1R-mediated brain-derived neurotrophic factor, intestinal protection suppression inflammation. We also discuss caveats combination with other peptide hormones.

Язык: Английский

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Neuronal diversity of neuropeptide signaling, including galanin, in the mouse locus coeruleus

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(31)

Опубликована: Июль 24, 2023

The locus coeruleus (LC) is a small nucleus in the pons from which ascending and descending projections innervate major parts of central nervous system. Its transmitter norepinephrine (NE). This system evolutionarily conserved, including humans, its functions are associated with wakefulness related to disorders, such as depression. Here, we performed single-cell ribonucleic acid-sequencing (RNA-seq) subdivide neurons LC (24 clusters total) into 3 NE, 17 glutamate, 5 γ-aminobutyric acid (GABA) subtypes, chart their neuropeptide, cotransmitter, receptor profiles. We found that NE expressed at least 19 neuropeptide transcripts, notably galanin (

Язык: Английский

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Shedding light on cholecystokinin’s role in hippocampal neuroplasticity and memory formation

Neuroscience & Biobehavioral Reviews, Год журнала: 2024, Номер 159, С. 105615 - 105615

Опубликована: Март 2, 2024

Язык: Английский

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Characterizing dysregulations via cell-cell communications in Alzheimer’s brains using single-cell transcriptomes

BMC Neuroscience, Год журнала: 2024, Номер 25(1)

Опубликована: Май 13, 2024

Abstract Background Alzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting 44 million people worldwide, leading to cognitive decline, memory loss, and significant impairment in daily functioning. The recent single-cell sequencing technology has revolutionized genetic genomic resolution by enabling scientists explore the diversity of gene expression patterns at finest resolution. Most existing studies have solely focused on molecular perturbations within each cell, but cells live microenvironments rather than isolated entities. Here, we leveraged large-scale publicly available single-nucleus RNA human prefrontal cortex investigate cell-to-cell communication healthy brains their AD. We uniformly processed snRNA-seq with strict QCs labeled canonical cell types consistent definitions from BRAIN Initiative Cell Census Network. From ligand receptor expression, built high-confidence network signaling differences between AD brains. Results Specifically, first performed broad pattern analyses highlight that biologically related normal rely largely overlapping networks brain exhibits irregular inter-mixing pathways. Secondly, more cell-type-centric analysis found excitatory neurons significantly increased communications inhibitory neurons, while other non-neuronal globally decreased theirs all cells. Then, delved deeper signaling-centric view, showing pathways CSF, TGFβ, CX3C are dysregulated type microglia/PVM endothelial neuronal for WNT pathway. Finally, after extracting 23 known risk genes, our intracellular revealed strong connection extracellular genes APP, APOE, PSEN1 TREM2, ABCA1, APP astrocytes microglia neurons. Conclusions In summary, novel advances technologies, show cellular regulated cell-type-specific manner improper regulation linked giving mechanistic intra- inter-cellular picture

Язык: Английский

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Potentiated GABAergic neuronal activities in the basolateral amygdala alleviate stress‐induced depressive behaviors

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 30(3)

Опубликована: Сен. 16, 2023

Major depressive disorder is a severe psychiatric that afflicts ~17% of the world population. Neuroimaging investigations depressed patients have consistently reported dysfunction basolateral amygdala in pathophysiology depression. However, how BLA and related circuits are implicated pathogenesis depression poorly understood.

Язык: Английский

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The dark sides of the GPCR tree ‐ research progress on understudied GPCRs

British Journal of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Фев. 10, 2024

Abstract A large portion of the human GPCRome is still in dark and understudied, consisting even entire subfamilies GPCRs such as odorant receptors, class C orphans, adhesion GPCRs, Frizzleds taste receptors. However, it undeniable that these bring an untapped therapeutic potential should be explored further. Open questions on span diverse topics deorphanisation, development tool compounds tools for studying well understanding basic signalling mechanisms. This review gives overview current state knowledge each understudied receptors regarding their physiological relevance, molecular mechanisms, endogenous ligands pharmacological tools. Furthermore, identifies some largest gaps addressed foreseeable future lists general strategies might helpful this process.

Язык: Английский

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Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease

BioFactors, Год журнала: 2024, Номер unknown

Опубликована: Май 22, 2024

Abstract Cholecystokinin (CCK) plays a key role in various brain functions, including both health and disease states. Despite the extensive research conducted on CCK, there remain several important questions regarding its specific brain. As result, existing body of literature subject is complex sometimes conflicting. The primary objective this review article to provide comprehensive overview recent advancements understanding central nervous system with emphasis elucidating CCK's mechanisms for neuroplasticity, exploring interactions other neurotransmitters, discussing significant involvement neurological disorders. Studies demonstrate that CCK mediates inhibitory long‐term potentiation (iLTP) excitatory (eLTP) Activation GPR173 receptor could facilitate iLTP, while B (CCKBR) facilitates eLTP. receptors' expression different neurons regulates activity, neurotransmitter release, plasticity, emphasizing modulating function. Furthermore, pivotal emotional states, Alzheimer's disease, addiction, schizophrenia, epileptic conditions. Targeting cell types circuits holds promise as therapeutic strategy alleviating these

Язык: Английский

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Basolateral amygdala parvalbumin and cholecystokinin-expressing GABAergic neurons modulate depressive and anxiety-like behaviors

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Окт. 5, 2024

Язык: Английский

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Advances in the Electrophysiological Recordings of Long-Term Potentiation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 7134 - 7134

Опубликована: Апрель 12, 2023

Understanding neuronal firing patterns and long-term potentiation (LTP) induction in studying learning, memory, neurological diseases is critical. However, recently, despite the rapid advancement neuroscience, we are still constrained by experimental design, detection tools for exploring mechanisms pathways involved LTP induction, ability of action signals. This review will reiterate LTP-related electrophysiological recordings mammalian brain nearly 50 years explain how excitatory inhibitory neural results have been detected described field- single-cell potentials, respectively. Furthermore, focus on describing classic model inhibition discuss neuron activity when neurons activated to induce LTP. Finally, propose recording under same conditions combining various technologies novel design suggestions future research. We discussed different types synaptic plasticity, potential astrocytes also deserves be explored future.

Язык: Английский

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Phoenixin knockout mice show no impairment in fertility or differences in metabolic response to a high‐fat diet, but exhibit behavioral differences in an open field test

Journal of Neuroendocrinology, Год журнала: 2024, Номер 36(10)

Опубликована: Май 10, 2024

Phoenixin (PNX) is a conserved secreted peptide that was identified 10 years ago with numerous studies published on its pleiotropic functions. PNX associated estrous cycle length, protection from high-fat diet, and reduction of anxiety behavior. However, no study had yet evaluated the impact deleting in whole animal. We sought to evaluate mouse model lacking parent gene, small integral membrane protein 20 (Smim20), resulting effect reproduction, energy homeostasis, anxiety. found Smim20 knockout mice normal fertility lengths. Consistent fertility, hypothalamii showed changes levels reproduction-related genes, but male some homeostasis-related such as melanocortin receptor 4 (Mc4r). When placed wildtype responded similarly, heterozygous gained slightly less weight. an open field test box, female traveled distance outer zone, indicating alterations or locomotor In summary, homozygous did not alter modestly alters few neuroendocrine genes response especially mice. it altered behavior test. therefore may be crucial for reproductive function weight, however, we cannot rule out possible compensatory mechanisms model. Understanding role physiology ultimately lead enhanced understanding involving this enigmatic peptide.

Язык: Английский

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