Electroacupuncture in rats normalizes the diabetes‐induced alterations in the septo‐hippocampal cholinergic system

Abstract

Diabetes induces early sufferance in the cholinergic septo‐hippocampal system, characterized by deficits in learning and memory, reduced hippocampal plasticity and abnormal pro‐nerve growth factor (proNGF) release from hippocampal cells, all linked to dysfunctions in the muscarinic cholinergic modulation of hippocampal physiology. These alterations are associated with dysregulation of several cholinergic markers, such as the NGF receptor system and the acetylcholine biosynthetic enzyme choline‐acetyl transferase (ChAT), in the medial septum and its target, the hippocampus. Controlled and repeated sensory stimulation by electroacupuncture has been proven effective in counteracting the consequences of diabetes on cholinergic system physiology in the brain. Here, we used a well‐established Type 1 diabetes model, obtained by injecting young adult male rats with streptozotocin, to induce sufferance in the septo‐hippocampal system. We then evaluated the effects of a 3‐week treatment with low‐frequency electroacupuncture on: (a) the expression and protein distribution of proNGF in the hippocampus, (b) the tissue distribution and content of NGF receptors in the medial septum, (c) the neuronal cholinergic and glial phenotype in the septo‐hippocampal circuitry. Twice‐a‐week treatment with low‐frequency electroacupuncture normalized, in both hippocampus and medial septum, the ratio between the neurotrophic NGF and its neurotoxic counterpart, the precursor proNGF. Electroacupuncture regulated the balance between the two major proNGF variants (proNGF‐A and proNGF‐B) at both gene expression and protein synthesis levels. In addition, electroacupuncture recovered to basal level the pro‐neurotrophic NGF receptor tropomyosin receptor kinase‐A content, down‐regulated in medial septum cholinergic neurons by diabetes. Electroacupuncture also regulated ChAT content in medial septum neurons and its anterograde transport toward the hippocampus. Our data indicate that repeated sensory stimulation can positively affect brain circuits involved in learning and memory, reverting early impairment induced by diabetes development. Electroacupuncture could exert its effects on the septo‐hippocampal cholinergic neurotransmission in diabetic rats, not only by rescuing the hippocampal muscarinic responsivity, as previously described, but also normalizing acetylcholine biosynthesis and NGF metabolism in the hippocampus.

Muscarinic receptors modulate Nerve Growth Factor production in rat Schwann-like adipose-derived stem cells and in Schwann cells

“…Distinct proNGF isoforms are expressed in mouse tissues, resulting from alternative splicing and/or activation of different promoters 5,43,44 ; as recently reported, proNGF-A has a pro-survival and differentiative effects in vitro 6 , whereas proNGF-B isoform acts as an apoptotic signal 7 . The longer variant proNGF-A (32-34 kDa) and the shorter variant proNGF-B (25-27 kDa) are produced in both CNS and PNS [43][44][45][46] . Our results suggest that muscarinic challenge promotes a proNGF-mediated neuroreparative response in dASCs, whilst cholinergic stimulation could improve neuronal survival and axon regeneration via proNGF-A/proNGF-B ratio modulation in glial cells.…”

Distribution in the brain and possible neuroprotective effects of intranasally delivered multi-walled carbon nanotubes

“…The arylation of the CNTs is a well-known and widely used approach to efficiently and conveniently modify the nanotubes 60,61 . counterpart, the precursor proNGF 42 , we delivered MWCNTs to both healthy and diabetic rats, the latter known to be affected by mild cognitive impairment associated with neurodegeneration and dysregulation of NGF production and activity, especially at hippocampal level [27][28][29]62 .…”

“…Rats early develop characteristic mild cognitive impairment, associated with neuronal sufferance 29 and dysregulation in the metabolism of protein markers of neurodegeneration, as protein tau and nerve growth factor (NGF) molecular system 27,28 .…”

“…Besides assessing their distribution in the brain parenchyma and their uptake by selected cell populations in the brain, we aimed to verify the neuroprotective potential of electroconductive CNTs. At this purpose we first performed a preliminary characterization of the displacement in the brain of both pristine and annealed electroconductive MWCNTs delivered via the olfactory route, then we investigated in vivo their neuroprotective potential, by delivering them to rats affected by early diabetic encephalopathy, characterized by mild neurodegeneration and poor neurocognitive performances [27][28][29] .…”

Machine Learning in Neuroimaging: A New Approach to Understand Acupuncture for Neuroplasticity

“…The long-term noxious stimulus, such as pain and depression, as well as regular exogenous interventions can reorganize the structure and function of the brain [6][7][8][9]. As the most widely used complementary therapy, acupuncture is considered to treat diseases via facilitating neural plasticity from multiple pathways, such as promoting endogenous neurogenesis, modulating synaptic plasticity, and regulating the secretion of neurotrophins and neurotransmitters, so as to affect the structural and functional plasticity of the brain [10][11][12][13].…”