ArticleBrain communications2026
JAK4D, a first-in-class thyrotropin-releasing hormone analogue, reverses scopolamine-induced memory deficits.
Article in Brain communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
There is a pressing unmet clinical and health economic need for effective drugs to treat cognitive impairment that occurs in neurodegenerative diseases. JAK4D is a first-in-class thyrotropin releasing hormone (TRH) analogue that overcomes the pharmacological limitations of thyrotropin releasing hormone and enables delivery of the long-recognized multifactorial neurotherapeutic actions of thyrotropin releasing hormone without inducing endocrine side effects. JAK4D is demonstrated to be neuroprotective and significantly reduce excitotoxic-induced hippocampal-dependent memory deficits in rat. In the present study, we used the scopolamine challenge test coupled with the novel object recognition test to evaluate the effect of JAK4D on scopolamine-induced recognition memory deficits in the male, Lister-Hooded rat. Scopolamine administration has been shown by others to mimic cholinergic and brain network disruption in neurodegenerative diseases. Although the scopolamine challenge test does not fully replicate the pathophysiology of neurodegenerative disease, such as Alzheimer's disease, it is a well-recognized acute pharmacological model for assessing the ability of pharmacological interventions to counteract memory deficits relevant to neurodegenerative diseases. In this model of cholinergic dysfunction, we also assessed the effects of thyrotropin releasing hormone, taltirelin (a degradation-stabilized thyrotropin releasing hormone analogue) and the acetylcholinesterase inhibitor, donepezil, as a positive reference compound. The discrimination (d2) index was used as the primary measure to assess the effect of treatment on scopolamine-induced performance deficit in the novel object recognition test. d2 is a standard well-recognized measure of discrimination between a novel and familiar object in the novel object recognition test, which advantageously takes into account individual differences in exploration levels. Across all investigations, JAK4D (1 mg/kg i.p.) significantly reversed scopolamine-induced recognition memory impairment (
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