Blunted pressor response to peripheral sensory afferent nerve stimulation in intracerebroventricular-streptozotocin injected rats

Auton Neurosci. 2025 Aug:260:103315. doi: 10.1016/j.autneu.2025.103315. Epub 2025 Jun 18.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder. It is characterized by synaptic loss and the increase of amyloid β (Aβ) in the brain often detrimentally affecting function. Brainstem is the key central integration site for sensory input from working skeletal muscle. Stimulation of skeletal muscle afferent fibers during muscle contraction increases blood pressure. However, whether AD alters or preserves the central processing of peripheral sensory afferent signals remains to be elucidated. Thus, we tested the hypothesis that the magnitude of the pressor response is functionally altered in intracerebroventricular-streptozotocin injected rats (ICV-STZ). Streptozotocin (3 mg/kg) was intracerebroventricularly injected into the lateral ventricle of male Sprague-Dawley rats. In parallel, a separate group of rats were treated with ICV saline as a vehicle control. Spatial learning and memory function were assessed using the Morris Water Maze behavioral test. Results demonstrate that ICV-STZ rats had a significantly longer time to reach a target platform compared to controls (P = 0.0046). ICV-STZ injection also significantly increased brainstem Aβ1-40 (P = 0.0082), but not Aβ1-42 (P = 0.0744). Further, the peak pressor and cardioaccelerator responses to tibial nerve stimulation were significantly attenuated in ICV-STZ rats compared to controls (ΔMAP: P = 0.0003, ΔHR: P = 0.0035). The findings suggest that the cardiovascular responses to electrical stimulation of sensory afferents are blunted in ICV-STZ rats.

Keywords: Amyloid β; And metaboreflex; Mechanoreflex; Sporadic Alzheimer's disease; Streptozotocin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Animals
  • Blood Pressure* / drug effects
  • Blood Pressure* / physiology
  • Brain Stem / drug effects
  • Brain Stem / metabolism
  • Electric Stimulation
  • Injections, Intraventricular
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Peripheral Nerves* / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin* / administration & dosage
  • Streptozocin* / pharmacology

Substances

  • Streptozocin
  • Amyloid beta-Peptides