Brain Peptide TLQP-62 Prevents Inflammation-Induced Memory Loss, Depression, and Anxiety in Mice

The neuropeptide fragment TLQP-62 (derived from the VGF protein) prevented inflammation-induced memory deficits, depression-like behavior, and anxiety-like behavior in mice when injected into the brain before an inflammatory challenge (LPS). TLQP-62 also reduced neuroinflammation and oxidative stress markers. Critically, when BDNF expression was knocked down using a viral vector, TLQP-62's protective effects were blocked — demonstrating that the peptide works through the BDNF/TrkB signaling pathway.

ICR mice received intracerebroventricular injection of TLQP-62 (2 μg/side) 1 hour before intraperitoneal LPS (0.5 mg/kg) to model inflammation-induced neuropsychiatric dysfunction. Behavioral tests included novel object recognition (memory), forced swim test and sucrose preference test (depression), and elevated zero maze (anxiety). Neuroinflammation and oxidative stress markers were measured. BDNF-shRNA lentivirus was used to knock down BDNF and test whether TLQP-62's effects depended on BDNF/TrkB signaling.

Neuroinflammation is increasingly recognized as a driver of depression, anxiety, and cognitive decline. This study identifies a specific neuropeptide (TLQP-62) that can protect against inflammation-induced brain dysfunction through BDNF signaling — a pathway already known to be central to antidepressant action. It suggests peptide-based approaches could offer a new therapeutic angle for neuropsychiatric conditions linked to inflammation.

The connection between inflammation and mental health is one of the most active areas of psychiatry research. Many patients with depression show elevated inflammatory markers, and traditional antidepressants don't work well for inflammation-driven depression. TLQP-62 represents a peptide-based approach that directly targets the BDNF pathway — the same pathway that existing antidepressants indirectly activate — but through a mechanism that also addresses neuroinflammation and oxidative stress.

Mouse study with invasive brain injection — not translatable to practical therapy. Single pretreatment design does not show whether the peptide works after inflammation has already started. The LPS model is a simplified acute inflammation model that may not replicate chronic neuroinflammatory conditions. TLQP-62 cannot cross the blood-brain barrier in its current form.