The involvement of protein kinase G inhibitor in regulation of apoptosis and autophagy markers in spatial memory deficit induced by Aβ

Abstract

The role of nitric oxide/protein kinase G (NO/PKG) in neurodegenerative disorders is controversial in different circumstances. PKG affects neurons both by itself and as a result of increased NO concentration. In this study, we examined the influence of PKG on spatial memory by intrahippocampal administration of three different concentrations of KT5823 as a PKG inhibitor. Morris water maze (MWM) was used for evaluation of behavioral alterations. We also measured the apoptosis and autophagy markers as two probable interfering pathways with PKG signaling by Western blot method. We found that in Aβ-pretreated rats, intrahippocampus infusions of 2.5, 5, and 10 μm/side of KT5823 led to a significant reduction in escape latency and traveled distance comparing to Aβ-treatment group. Our molecular findings indicated that KT5823 could induce autophagy and attenuate apoptotic markers at distinct doses. Here, we can conclude that in addition to other parameters, apoptosis, and autophagy in part have damaging and protective roles, respectively, in PKG signaling mechanisms. As autophagy-related proteins lose their functions in neurodegenerative diseases, we can suggest that autophagy can be one of the therapeutic aims for remedy of Alzheimer's disease.

Potential therapeutic action of natural products from traditional Chinese medicine on Alzheimer's disease animal models targeting neurotrophic factors

“…Pathogenesis of AD is extremely complicated. During the pathological process of AD, loss of cholinergic neurons and synapses, Aβ cascade, neuroinflammation, tau hyperphosphorylation, mitochondrial dysfunction, and NTF reduction are all important events . Therefore, in the treatment of AD, multicomponent and multitarget drugs, such as TCM, may be advantageous over single‐target drugs .…”

Toxic Substance-induced Hippocampal Neurodegeneration in Rodents as Model of Alzheimer’s Dementia

“…Number of article Route of Administration ICV IP Oral Sub-cutaneous Amyloid β** 35 [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34]. [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47] 35 0 0 0 Streptozotocin** 16 [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63] 16...…”

Estrogen deficiency induces memory loss via altered hippocampal HB-EGF and autophagy

“…Hence, for both E2-dependent and -independent conditions, mitochondrial dynamics presumably regulates the typical functions of HB-EGF, viz., survival, mitogenesis, antiexcitotoxicity, and so forth, particularly in hippocampal neurons. Likewise, for amyloid beta toxicity, aging, learning memory impairments (Shariatpanahi et al 2016, Huang et al 2018, and so forth marked by hippocampal autophagy, an intermediate involvement of HB-EGF seems worth exploring.…”