Upregulation of microRNA‐196a improves cognitive impairment and alleviates neuronal damage in hippocampus tissues of Alzheimer's disease through downregulating LRIG3 expression

Abstract

Purpose This study is launched to uncover the inner function of microRNA‐196a (miR‐196a) on cognitive dysfunction and neuronal damage in Alzheimer's disease (AD) rats through regulating the PI3K/Akt signaling pathway. Methods The establishment of AD rat model was performed by a microinjection of Aβ25‐35. miR‐196a and LRIG3 expression was detected, and the putative binding site between them was also determined. The spatial learning and memory capability, the hippocampal neurons ultrastructure as well as the survival, and apoptosis of hippocampal neurons of rats were observed. The expression of apoptosis‐associated protein, oxidative stress index, and inflammatory factors as well as the PI3K/Akt pathway‐related factors was determined. Results Initially, decreased miR‐196a and increased LRIG3 were exhibited in hippocampus tissues of AD rats. In addition, restored miR‐196a and deleted LRIG3 ameliorated spatial learning and memory capability, suppressed the pathological injury, induced the survival, and suppressed the apoptosis of hippocampal neurons, as well as inhibited oxidative stress injury together with inflammatory injury in AD rats. Furthermore, upregulation of miR‐196a activated the PI3/Akt pathway in AD rats. Conclusion This current study suggests that upregulation of miR‐196a and downregulation of LRIG3 improve cognitive impairment and alleviate neuronal damage in hippocampus tissues in AD rats via the modulation of the PI3K/Akt pathway.

Implications of miR-148a-3p/p35/PTEN signaling in tau hyperphosphorylation and autoregulatory feedforward of Akt/CREB in Alzheimer’s disease

“… 9 , 10 It is hypothesized that abnormal regulation of miRNA-targeted networks plays a key role in AD pathological processes via regulation of genes involving Aβ overproduction, 11 , 12 , 13 tau hyperphosphorylation, 14 , 15 glial-activation-induced neuroinflammation, 16 , 17 synaptic dysfunction, 18 , 19 and neuronal apoptosis. 20 , 21 Despite reported involvement of novel miRNAs in AD pathogenesis, the identity of sensitive mRNAs involved in the diagnosis, treatment, and pathophysiological implications of AD remains unclear.…”

Nicotine abolishes memory‐related synaptic strengthening and promotes synaptic depression in the neurogenic dentate gyrus of miR‐132/212 knockout mice

“…miRNAs also influence several vital neurodevelopmental and adult brain neuronal processes 14,18,19,21 . Moreover, alterations of the miRNAs activity is associated with Alzheimer's 27–35 and Parkinson's diseases 11 . Understanding of the miRNAs systems of neuronal regulation is thus timely and relevant.…”

“…For example, miRNAs are critical for neural development 21 and adult neurogenesis, 14,18,19 and memory‐related synaptic plasticity 22,23 . Dysregulation of miRNAs activity is further associated with a wide variety of severely debilitating human neurodegenerative conditions such as epilepsy, 24–26 Alzheimer's 27–35 and Parkinson's diseases 11 …”

miR‑132 improves the cognitive function of rats with Alzheimer's disease by inhibiting the MAPK1 signal pathway

“…Lin et al (30) used Osthole to upregualte miRNA-101a-3p. Several miRNAs have been reported to be involved in a variety of diseases (16)(17)(18)(19). Because of their stability and endogenous nature, miRNAs may be used as treatment options in AD (31).…”

“…Numerous biological processes and >60% human genes are regulated by microRNAs (miR) than can be found in most body tissues, including brain tissues, cerebrospinal fluid and serum ( 15 ). Dysregulation of miRNA is therefore crucial in neurodegenerative diseases ( 16 ). Previous in vitro and in vivo studies have explored the role of miRNAs in the pathogenesis of AD, and demonstrated that miR-92a-3p, miR-181c-5p and miR-210-3p, miRNA-132, miRNA-107 are in abnormal high or low expression level in the brains of patients with AD ( 17-19 ).…”