Non-Invasive Brain Stimulation Improves Episodic Memory by Recovering Bloodbrain-Barrier Leakage in intracerebroventricular Streptozotocin Injected Rat Model of Alzheimer’s Disease
Journal Title: The 2nd Annual Meeting of International Center for Neuroscience Research - Year 2021, Vol 2, Issue 1
Abstract
Intracerebroventricular streptozotocin (STZ) injection at 3mg/kg of b/w is reported to induce Alzheimer disease (AD) like pathology (Frölich et al., 1999; Lannert & Hoyer, 1998; Nitsch & Hoyer, 1991; Salkovic-Petrisic et al., 2011), where it causes an insulin resistance brain state. Cerebral vessel and blood brain barrier (BBB) pathology poses a major risk in AD. Inflammatory responses adjacent to and failure of Aβ clearance through BBB is known to be prominent in the AD pathophysiology. Transcranial magnetic field stimulation is shown to be promising in AD patients, however, mechanistic effect of low intensity magnetic field stimulation are not studied well. Therefore, in present study we have looked into the effect of 17.96µT for 2hr/day for 60 days magnetic field (MF) stimulation at neurovascular unit (NVU), expression of Glut3, and PI3K in hippocampus and level of APOε4 in serum. In addition, episodic memory retention at 60th day post-stimulation measured using one trial object recognition task. Total 48 rats were recruited in order to complete the objectives and they were randomly divided into five groups: Control, Sham (i.c.v. aCSF), AD (i.c.v. STZ), Sham+MF (i.c.v. aCSF and MF stimulation), AD+MF (i.c.v. STZ and MF simulation). Animals were provided with ad libitum access to food and water, all the experiments were performed under permission from IAEC (file no. 937/IAEC/2016). Results revealed that there was a significant reduction in recognition as well as discrimination index in AD group as compared to Sham (p<0.001), Sham+MF (p<0.01) and AD+MF (p<0.0001). Suggesting a severe impairment in episodic memory on 60th day post-injection of STZ, which was improved after magnetic field stimulation. We found a downregulation in the expression of Glut3 transporter of glucose and γ85 subunit of PI3K in the stratum radiatum and stratum pyramidale of both CA1 as well as CA3 subfield of hippocampus in AD group in comparison to Control, Sham group. Whereas it was shown to be upregulated in Sham+MF and AD+MF group. More interestingly, we found expression of Glut3 transporter in the cerebral vessels. In the electron-microscopic examination of hippocampal samples, we found invasion of ramified microglia in NVU as well as loss of synaptic density at 60th day post-injection of STZ, which was recovered after magnetic field stimulation. Furthermore, serum level of APOε4 was shown to be significantly increased in AD group as compared to Control, Sham, Sham+MF (p= 0.028) groups. Hence, this work put forward that cognitive impairment in i.c.v. STZ injected rats at 60th day is associated with disruption of blood brain barrier and brain metabolism, which was partially improved upon low-frequency MF stimulation.
Authors and Affiliations
Avishek Roy*, Binney Sharma, Ritesh Neetam, Tapas Chandra Nag, Suman Jain
Keywords
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