Antagonism of Histamine H3 receptors Alleviates Pentylenetetrazole-Induced Kindling and Associated Memory Deficits by Mitigating Oxidative Stress, Central Neurotransmitters, and c-Fos Protein Expression in Rats.
Alaa AlachkarSheikh AzimullahMohamed LotfyErnest AdeghateShreesh K OjhaRami BeiramDorota ŁażewskaKatarzyna Kieć-KononowiczBassem SadekPublished in: Molecules (Basel, Switzerland) (2020)
Histamine H3 receptors (H3Rs) are involved in several neuropsychiatric diseases including epilepsy. Therefore, the effects of H3R antagonist E177 (5 and 10 mg/kg, intraperitoneal (i.p.)) were evaluated on the course of kindling development, kindling-induced memory deficit, oxidative stress levels (glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)), various brain neurotransmitters (histamine (HA), acetylcholine (ACh), γ-aminobutyric acid (GABA)), and glutamate (GLU), acetylcholine esterase (AChE) activity, and c-Fos protein expression in pentylenetetrazole (PTZ, 40 mg/kg) kindled rats. E177 (5 and 10 mg/kg, i.p.) significantly decreased seizure score, increased step-through latency (STL) time in inhibitory avoidance paradigm, and decreased transfer latency time (TLT) in elevated plus maze (all P < 0.05). Moreover, E177 mitigated oxidative stress by significantly increasing GSH, CAT, and SOD, and decreasing the abnormal level of MDA (all P < 0.05). Furthermore, E177 attenuated elevated levels of hippocampal AChE, GLU, and c-Fos protein expression, whereas the decreased hippocampal levels of HA and ACh were modulated in PTZ-kindled animals (all P < 0.05). The findings suggest the potential of H3R antagonist E177 as adjuvant to antiepileptic drugs with an added advantage of preventing cognitive impairment, highlighting the H3Rs as a potential target for the therapeutic management of epilepsy with accompanied memory deficits.
Keyphrases
- oxidative stress
- diabetic rats
- temporal lobe epilepsy
- cognitive impairment
- working memory
- traumatic brain injury
- dna damage
- high glucose
- breast cancer cells
- ischemia reperfusion injury
- induced apoptosis
- cerebral ischemia
- drug induced
- early stage
- amyotrophic lateral sclerosis
- human health
- white matter
- multiple sclerosis
- cell cycle arrest
- cell proliferation
- nitric oxide
- mouse model
- pi k akt
- endoplasmic reticulum stress
- blood brain barrier
- signaling pathway
- resting state
- stress induced