PARIN5, a Novel Thrombin Receptor Antagonist Modulates a Streptozotocin Mice Model for Diabetic Encephalopathy

Figures

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  Figure 1. Elevated levels of serum NfL in diabetic mice are normalized by PARIN5 treatment: serum levels of NfL as a marker for neuronal damage are elevated in diabetic mice compared to the control. No significant (NS) change was measured in diabetic mice treated with PARIN5. Data are represented as mean ± SEM, * p < 0.05. Control = 10, STZ = 17, STZ + PARIN5 = 6.

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  Figure 2. Thrombin activity levels in the hippocampus, optic nerve, sciatic nerve, and skin: Upper panel- CNS-derived tissues. (A) hippocampal thrombin activity was significantly elevated in STZ mice treated with PARIN5 compared to untreated controls and controls treated with PARIN5. (B) Optic nerve thrombin activity was significantly elevated in STZ with and without PARIN5 treatment compared to the control. Lower panel- PNS-derived tissues. Thrombin activity was significantly elevated in STZ compared to control in both sciatic nerve (C) and skin (D). Data are represented as mean ± SEM, * p < 0.04, ** p < 0.003, *** p < 0.0003. STZ = 10–17, STZ + PARIN5 = 6–11, PARIN = 9–10.

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  Figure 3. Open Field test: There were no significant differences between STZ diabetic and healthy mice in parameters of ambulation, including velocity (A) and frequency of center crossing (B). Center duration, divided by center frequency, was significantly longer in STZ diabetic mice compared to healthy controls, suggesting slower, more encephalopathic mice (C). Rearing behavior was significantly reduced in diabetic STZ mice compared to healthy control (D), supporting elevated anxiety as a possible manifestation of encephalopathy. Data are represented as mean ± SEM, * p < 0.05. Control = 9, STZ = 4, STZ + PARIN5 = 6.

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  Figure 4. Novel object recognition test: there was no significant difference between healthy controls, STZ diabetic mice, and STZ diabetic mice treated with PARIN5 in either velocity (A) or discrimination index (B). Data are represented as mean ± SEM.

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  Figure 5. Brain expression of inflammatory and coagulation factors following PARIN5 treatment: expression of TNF-α (A) and FX (B) genes was significantly elevated in diabetic mice compared to control. Expression of prothrombin (PT) was significantly elevated in diabetic mice and was even higher in PARIN5-treated mice (C). Expression of PAR1 was not significantly affected by diabetes or PARIN5 treatment in diabetic mice (D). Data are represented as mean ± SEM, * p < 0.05, ** p < 0.01. Control = 8–9, STZ = 4, STZ + PARIN5 = 3.

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  Figure 6. Experiment timeline. Created with BioRender.com.