Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and...

Area of Science:

• Neuroscience
• Neurobiology
• Metabolic Disorders

Background:

• Disrupted copper (Cu) homeostasis is linked to neurodegenerative diseases.
• Olfactory dysfunction is an early symptom in some neurodegenerative conditions.

Purpose of the Study:

• To investigate the impact of copper dyshomeostasis on olfactory function.
• To examine alterations in adult neurogenesis and neurochemical balance due to copper imbalance.

Main Methods:

• Established rat models of copper deficiency (CuD) and copper overload (CuO).
• Administered Cu-restricted diets, Cu chelator (ammonium tetrathiomolybdate), and excess Cu.
• Assessed olfactory function using the buried pellet test.
• Analyzed neural proliferation, stem cells, and neuronal differentiation in the olfactory bulb (OB) and subventricular zone (SVZ).
• Measured neurochemical levels (GABA, DOPAC, HVA, 5-HT) and mRNA expression of Cu transport proteins.

Main Results:

• Both CuD and CuO prolonged latency in the buried pellet test, indicating olfactory dysfunction.
• CuD increased neural proliferation and stem cells in the SVZ and OB, while CuO had opposite effects.
• CuO increased GABA in the OB.
• Both CuD and CuO reduced DOPAC, HVA, 5-HT, and dopamine turnover rate in olfactory-related brain areas.
• Altered mRNA expression of Cu transport and storage proteins was observed.

Conclusions:

• Systemic copper dyshomeostasis is associated with olfactory dysfunction.
• Altered adult neurogenesis in the SVZ-RMS-OB pathway and neurochemical imbalances contribute to olfactory deficits.