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Advanced Neurologyurology
Advanced Ne MiR-195 regulates MS-dCA1 neural circuit in CBH rat

occurs before mild cognitive impairment (MCI), is an early whether and how miR-195 modulates the function of
clinical stage shared by both AD and VaD . The previous MS-dCA1 neural circuit under CCH condition.
[3]
studies have shown that CCH leads to cognitive decline and Here, using the in vivo electrophysiological recording
induces a series of AD-like pathological changes [4-6] , such and neurotracing technique, we demonstrated for the
as Aβ deposition, tau hyperphosphorylation, neuronal 1 time that CCH induced the downregulation of miR-195
st
death, microglial polarization, and synaptic dysfunction expression in the MS region and inhibited hippocampal
in the hippocampus and cortex [7-11] . Furthermore, our rhythmogenesis in the dCAl region by reducing the release
recent study found that CCH also impairs the function of of ACh. The mechanism is that miR-195 leads to the loss
the medial septum (MS)-dorsal hippocampal CA1 (dCA1) of cholinergic and GABAergic neurons in the MS region.
(MS-dCA1) neural circuit and reduces hippocampal Upregulation of miR-195 expression can rescue MS-dCA1
presynaptic neurotransmitter release in rats . However, neural circuit damage and decline of spatial memory in
[12]
the mechanism remains unknown. CCH rats. Collectivity, the present data provide further
There are highly interconnected cholinergic, evidence that miR-195 may be a valuable candidate for the
GABAergic, and a small number of glutamatergic neurons miRNA-based treatment of dementia.
in the MS region of the basal forebrain that can project
to glutamatergic pyramidal neurons and GABAergic 2. Materials and methods
interneurons in the dCA1 region. This process can modulate 2.1. Animals
the excitability of hippocampal dCA1 neurons [13-15] . The Adult male Sprague-Dawley (SD) rats (250–280 g)
MS-dCA1 neural circuit is essential for various behavioral were bought from the Animal Center of the Second
situations because it controls the rhythm of hippocampal Affiliated Hospital of Harbin Medical University,
electrical activity by regulating the release of acetylcholine Harbin, Heilongjiang Province, China. The rats were
(ACh) in the hippocampus . Importantly, it has been accommodated in a rearing room at 24°C, 55% humidity,
[16]
found that the degeneration of nerve fibers in the MS-dCA1 and a 12-h dark/light cycle with adequate food and water.
circuit occurs earlier than neuronal death in AD or VaD All animal experiments were approved by the Ethics
[17]
patients . This phenomenon suggests that activation Committee of Harbin Medical University (Approval No:
of MS-dCA1 neural circuit may be a good strategy for IRB3199620). All procedures conformed to Directive
treating CCH-induced cognitive impairment. 2010/63/EU of the European Parliament.
Clinically, cholinesterase inhibitors are the only class
of drugs that treat early AD by blocking hippocampal 2.2. Permanent bilateral common carotid artery
ACh degradation and provide temporary symptom relief. occlusion
Finding a drug targeting on multi-targets of AD pathologies The surgical procedure of 2VO rats, which was conducted
has become a consensus. The main characteristic of according to our published work, is briefly described
microRNAs (miRNAs) is that they regulate protein as follows: Rats were anesthetized with chloral hydrate
expression at the post-transcriptional level by targeting (300 mg/kg) and maintained with isoflurane (0.5–1.0%).
multiple genes [18,19] . Many miRNAs have been found to The bilateral common carotid arteries of rats were ligated
participate in AD pathological process by regulating with 5-0 sterile silk thread, and the arteries were cut with
classical amyloid precursor protein (APP) and β-site APP ophthalmic scissors 5 min later. The incision was sutured
cleaving enzyme 1 (BACE1) expressions [20-23] . Of note, and disinfected at the end of the procedure. After the rats
it has been reported that miR-195 is involved in various were fully awake, they were put into home cages and kept
AD-like pathologies induced by CCH through regulating for another 8 weeks for all subsequent experiments .
[7]
the expression of multiple proteins, such as APP/BACE1, as
well as the N-APP/DR6/caspase pathway and the CX3CL1/ 2.3. Construction of lentivirus vectors
CX3CR1 signaling pathway [7-10] , and protected against The procedure for constructing lentivirus vectors has
ApoE4-induced cognitive abnormalities and lysosomal also been described in our previous work . Lenti-pre-
[7]
deficiencies in mice . Furthermore, miR-195 attenuates miR-195, lenti-AMO-195, and lenti-NC were created by
[24]
cerebral ischemia-reperfusion injury through the PTEN- GeneCopoeia Inc. (Rockville, MD, USA).
AKT and KLF5-mediated JNK signaling pathway in rats
with ischemic stroke [25,26] . Recently, Cheng et al. reported 2.4. Stereotactic brain injection procedure
that miR-195 could also protect against ischemic and The rats were intraperitoneally injected with 10% chloral
hemorrhagic stroke by protecting the neurovasculature hydrate after fasting for 8 h. T-shaped incision was made
and promoting neurogenesis . However, it is unclear in the rat scalp, and the periosteum was peeled off to
[27]

Volume 1 Issue 2 (2022) 2 https://doi.org/10.36922/an.v1i2.116