Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction.

Area of Science:

• Neuroscience
• Urology

Background:

• Spinal cord injury (SCI) and cyclophosphamide (CYP)-induced cystitis significantly impact lower urinary tract (LUT) function.
• These conditions lead to neurochemical, electrophysiological, and anatomical changes, potentially causing neural plasticity and reorganization of the micturition reflex.
• Alterations in neurotrophic factors within the urinary bladder are hypothesized to mediate these plastic changes.

Purpose of the Study:

• To investigate changes in urinary bladder neurotrophic factor messenger RNA (mRNA) and protein expression following SCI and CYP-induced cystitis.
• To determine the correlation between neurotrophic factor mRNA and protein levels in the urinary bladder under these experimental conditions.
• To explore the potential role of these neurotrophic factors in the neural plasticity underlying LUT dysfunction after SCI or cystitis.

Main Methods:

• A ribonuclease protection assay was employed to quantify mRNA levels of beta-nerve growth factor (betaNGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in rat urinary bladders.
• Experimental groups included acute (4 days) and chronic (4-6 weeks) SCI, as well as acute and chronic CYP-induced cystitis.
• Nerve growth factor (NGF) protein levels were also measured, and the correlation between NGF mRNA and protein was assessed.

Main Results:

• Both SCI and CYP-induced cystitis caused significant changes in urinary bladder neurotrophic factor mRNA levels, with varying magnitudes between paradigms.
• Acute SCI led to the most substantial increases in neurotrophic factor mRNA, particularly BDNF (78-fold) and betaNGF (21-fold).
• Significant increases in neurotrophic factor mRNA were observed in both acute and chronic cystitis models. However, urinary bladder NGF protein decreased in cystitis despite increased mRNA, and NGF mRNA-protein correlation was observed only at later time points in SCI.

Conclusions:

• Urinary bladder neurotrophic factor mRNA expression is significantly altered following SCI and cystitis, suggesting a role in LUT dysfunction.
• The dissociation between NGF mRNA and protein levels in cystitis, and the temporal correlation in chronic SCI, may indicate complex regulatory mechanisms, possibly involving retrograde axonal transport.
• These findings highlight the dynamic changes in neurotrophic factors within the urinary bladder following injury or inflammation, contributing to the understanding of neural plasticity in LUT control.