Guggulsterone Mediated JAK/STAT and PPAR-Gamma Modulation Prevents Neurobehavioral and Neurochemical Abnormalities in Propionic Acid-Induced Experimental Model of Autism

Abstract

Autism spectrum disorder is a neurodevelopmental disorder marked by repetitive behaviour, challenges in verbal and non-verbal communication, poor socio-emotional health, and cognitive impairment. An increased level of signal transducer and activator of transcription 3 (STAT3) and a decreased level of peroxisome proliferator-activated receptor (PPAR) gamma have been linked to autism pathogenesis. Guggulsterone (GST) has a neuroprotective effect on autistic conditions by modulating these signalling pathways. Consequently, the primary objective of this study was to examine potential neuroprotective properties of GST by modulating JAK/STAT and PPAR-gamma levels in intracerebroventricular propionic acid (ICV PPA) induced experimental model of autism in adult rats. In this study, the first 11 days of ICV-PPA injections in rats resulted in autism-like behavioural, neurochemical, morphological, and histopathological changes. The above modifications were also observed in various biological samples, including brain homogenate, CSF, and blood plasma. GST was also observed to improve autism-like behavioural impairments in autistic rats treated with PPA, including locomotion, neuromuscular coordination, depression-like behaviour, spatial memory, cognition, and body weight. Prolonged GST treatment also restored neurochemical deficits in a dose-dependent manner. Chronic PPA administration increased STAT3 and decreased PPAR gamma in autistic rat brain, CSF, and blood plasma samples, which were reversed by GST. GST also restored the gross and histopathological alterations in PPA-treated rat brains. Our results indicate the neuroprotective effects of GST in preventing autism-related behavioural and neurochemical alterations.

Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis

“…In tissue samples, glutamate was measured using Alam and coworkers’ method after derivatization with o-phthalaldehyde/-mercaptoethanol (OPA/-ME). The ng/mg protein represents the glutamate concentration in rat brain homogenate [ 62 , 73 ]. A diagnostic kit was used to assess acetylcholine levels (Krishgen diagnostics, India).…”

Forskolin, an Adenylcyclase/cAMP/CREB Signaling Activator Restoring Myelin-Associated Oligodendrocyte Destruction in Experimental Ethidium Bromide Model of Multiple Sclerosis

“…After centrifuging the homogeneous material at 10.500× g for 15 min, the supernatant was separated. The whole-brain homogenate was used to assess oxidative stress, neurotransmitter, neurochemical, and cellular and molecular changes [ 35 ].…”

Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity

“…Hematoxylin and eosin staining was used on the sections, and morphology was analysed using a fluorescent microscope (Type 102 M; 100 × Magnification). The properties and density of the normal neuronal population (Oligodendrocytes, microglial cells, and area of necrosis) in the cerebral cortex were observed blindly using a fluorescent microscope with a reticular consolidated eyepiece at a magnification of 100× [29].…”

“…GLP-1 and its analogues reduce neurological dysfunctions by promoting neurogenesis through cAMP production [24], enhancing neurotransmission [25], and promoting dendritic morphogenesis [26] as well as synaptic plasticity [27]. Furthermore, these analogues prevent inappropriate microglia-mediated cytokine production, apoptosis [28,29], oxidative stress [30], and axonal transport abnormalities [31].…”