How TRPC Channels Modulate Hippocampal Function

Gualdani, Roberta; Gailly, Philippe

doi:10.3390/ijms21113915

Cited by 13 publications

(17 citation statements)

References 171 publications

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“…Studies have indicated that TRP channels, ubiquitously expressed throughout the brain, 10 play a key role in the regulation of physiological functions, as well as in pathological ones, including cardiovascular, neurological, metabolic, or neoplastic disorders. [6][7][8]41,42 Moreover, mutations in genes encoding TRP channels are the cause of several inherited diseases in humans (the so-called 'TRP channelopathies') that affect the cardiovascular, renal, skeletal, and nervous systems. 43 Since TRP channels can be opened and activated in response to various stimuli, their hyperactivation can induce neuronal loss and excitotoxicity, which are closely associated with neurodegenera- tive diseases.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, they are involved in the basic hippocampal function, such as different memory and learning processes. 7 TRP ions channels family is involved in sensory (pheromone signaling, taste transduction, nociception, and temperature sensation) and homeostatic functions (such as Ca 2+ and Mg 2+ reabsorption and osmoregulation), as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases.…”

Section: Introductionmentioning

confidence: 99%

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Ion channels alterations in the forebrain of high-fat diet fed rats

Roy¹,

Martinelli

Moruzzi

et al. 2021

Eur J Histochem

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Evidence suggests that transient receptor potential (TRP) ion channels dysfunction significantly contributes to the physiopathology of metabolic and neurological disorders. Dysregulation in functions and expression in genes encoding the TRP channels cause several inherited diseases in humans (the so-called ‘TRP channelopathies’), which affect the cardiovascular, renal, skeletal, and nervous systems. This study aimed to evaluate the expression of ion channels in the forebrain of rats with diet-induced obesity (DIO). DIO rats were studied after 17 weeks under a hypercaloric diet (high-fat diet, HFD) and were compared to the control rats with a standard diet (CHOW). To determine the systemic effects of HFD exposure, we examined food intake, fat mass content, fasting glycemia, insulin levels, cholesterol, and triglycerides. qRT-PCR, Western blot, and immunochemistry analysis were performed in the frontal cortex (FC) and hippocampus (HIP). After 17 weeks of HFD, DIO rats increased their body weight significantly compared to the CHOW rats. In DIO rats, TRPC1 and TRPC6 were upregulated in the HIP, while they were downregulated in the FC. In the case of TRPM2 expression, instead was increased both in the HIP and in the FC. These could be related to the increase of proteins and nucleic acid oxidation. TRPV1 and TRPV2 gene expression showed no differences both in the FC and HIP. In general, qRT-PCR analyses were confirmed by Western blot analysis. Immunohistochemical procedures highlighted the expression of the channels in the cell body of neurons and axons, particularly for the TRPC1 and TRPC6. The alterations of TRP channel expression could be related to the activation of glial cells or the neurodegenerative process presented in the brain of the DIO rat highlighted with post synaptic protein (PSD 95) alterations. The availability of suitable animal models may be useful for studying possible pharmacological treatments to counter obesity-induced brain injury. The identified changes in DIO rats may represent the first insight to characterize the neuronal alterations occurring in obesity. Further investigations are necessary to characterize the role of TRP channels in the regulation of synaptic plasticity and obesity-related cognitive decline.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ion channels alterations in the forebrain of high-fat diet fed rats

Roy¹,

Martinelli

Moruzzi

et al. 2021

Eur J Histochem

View full text Add to dashboard Cite

show abstract

“…Based on structure–function relationships, the TRPC family is grouped into four subsets: TRPC1, TRPC2, TRPC3/6/7 and TRPC4/5. Besides functioning as homotetramers, combinations of different TRPC subunits can form heterotetrameric complexes, which may regulate responses to neuropeptides and neurotransmitters with different properties than homotetrameric TRPC channels [ 28 ]. For instance, TRPC6 has high sequence homology with TRPC3 and TRPC7 subunits, and may form a heterotetramer with TRPC3 [ 29 ].…”

Section: Trpc6mentioning

confidence: 99%

Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

Shekhar

Liu

Wang

et al. 2021

IJMS

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Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates the cAMP (adenosine 3’,5’-cyclic monophosphate) response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of N-methyl-D-aspartate (NMDA) receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells, such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood–brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

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“…Based on struc-ture-function relationships, the TRPC family is grouped into four subsets: TRPC1, TRPC2, TRPC3/6/7 and TRPC4/5. Besides functioning as homotetramers, combinations of different TRPC subunits can form heterotetrameric complexes, which may regulate responses to neuropeptides and neurotransmitters with different properties than homotetrameric TRPC channels [28]. For instance, TRPC6 has high sequence homology with TRPC3 and TRPC7 subunits, and may form a heterotetramer with TRPC3 [29].…”

Section: Trpc6mentioning

confidence: 99%

Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

Shekhar¹,

Liu²,

Wang³

et al. 2021

Preprint

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Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates cAMP response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of NMDA receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood-brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

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How TRPC Channels Modulate Hippocampal Function

Cited by 13 publications

References 171 publications

Ion channels alterations in the forebrain of high-fat diet fed rats

Ion channels alterations in the forebrain of high-fat diet fed rats

Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

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