Heat Acclimation in Mice Requires Preoptic BDNF Neurons and Postsynaptic Potentiation

Neurology Life Sciences Cell Biology Medicine
heat acclimation BDNF neurons postsynaptic potentiation anxiety thermoregulation

Academic Background

Heat Acclimation (HA) is a key adaptive response in mammals to repeated exposure to high temperatures, essential for improving cardiovascular function, thermal comfort, and exercise capacity. However, due to the lack of genetically tractable models, the molecular and neural mechanisms underlying HA have not been fully elucidated. Previous studies have shown that Brain-Derived Neurotrophic Factor (BDNF) in the Preoptic Area (POA) is involved in heat defense, but its specific role in HA remains unclear. Therefore, this study aimed to explore the role of BDNF neurons in HA and their downstream neural circuit mechanisms using a mouse model.

Source of the Paper

This study was conducted by Baoting Chen, Cuicui Gao, and other researchers from institutions such as ShanghaiTech University and Shanghai University of Traditional Chinese Medicine. The paper was received on October 24, 2024, accepted on December 7, 2024, and published online on December 26, 2024, in the journal Cell Research, with the DOI 10.1038/s41422-024-01064-6.

Research Process and Results

1. Establishment of the Heat Acclimation Model

The researchers first evaluated three different HA protocols and ultimately identified an effective one: exposing mice to 38°C for 2 hours daily over 10 consecutive days. This protocol significantly improved heat tolerance in mice, as evidenced by a moderate rise in core body temperature (Tcore) during subsequent high-temperature exposures. Additionally, water intake significantly increased during HA, while food intake and body weight remained unchanged.

2. Physiological Effects of Heat Acclimation

After HA, mice exhibited extended Tcore tolerance in the Heat Tolerance Test (HTT) at 40°C and showed significantly reduced anxiety behaviors. Specifically, exploratory behaviors increased in the Open Field Test (OFT) and Elevated Plus Maze (EPM). However, HA did not affect thermal preference or nociceptive heat perception.

3. Role of BDNF Neurons

The study found that HA significantly increased BDNF expression in the Medial Preoptic Area (MPO). Furthermore, BDNF neurons in the MPO (MPOBDNF) exhibited higher intrinsic heat sensitivity after HA, with the proportion of Warm-Sensitive Neurons (WSNs) increasing from 22.7% to 43.3%. By inhibiting MPOBDNF neurons, the researchers observed that the improvements in Tcore and anxiety induced by HA were almost completely abolished, indicating the critical role of these neurons in HA.

4. Exploration of Downstream Neural Circuits

The researchers further discovered that MPOBDNF neurons mediate HA effects by projecting to the Dorsomedial Hypothalamus (DMH) and Rostral Raphe Pallidus (rRPa). Blocking these projection pathways nearly eliminated the improvements in Tcore and anxiety induced by HA. Additionally, BDNF, acting through its receptor TrkB in the DMH, enhances excitatory synaptic connections between MPOBDNF and DMH neurons, thereby promoting the anxiolytic effects of HA.

5. Mechanisms of Synaptic Plasticity

The study revealed that HA enhances excitatory synaptic transmission in the MPOBDNF→DMH pathway through the BDNF-TrkB signaling pathway, as evidenced by increased amplitudes of Excitatory Postsynaptic Currents (EPSCs). This synaptic plasticity change primarily depends on increased postsynaptic ion conductance rather than changes in presynaptic glutamate release probability.

Conclusions and Significance

This study is the first to reveal the critical role of BDNF neurons in HA in mice and elucidate the specific mechanisms of the MPOBDNF→DMH/rRPa neural circuit in HA. The findings show that HA enhances BDNF expression in the MPO and the intrinsic heat sensitivity of neurons, strengthening excitatory synaptic connections between MPOBDNF and DMH neurons, thereby improving heat tolerance and anxiety behaviors. This research not only deepens our understanding of the physiological mechanisms of HA but also provides new theoretical foundations for heat stress management and exercise optimization.

Research Highlights

  1. Innovative Model: This study established a simple and reproducible mouse HA model for the first time, providing an important tool for future research.
  2. Key Mechanism Revealed: The study identified the central role of BDNF neurons and their downstream neural circuits in HA, filling a knowledge gap in this field.
  3. Mechanism of Synaptic Plasticity: The research elucidated the specific mechanism by which the BDNF-TrkB signaling pathway promotes synaptic plasticity through enhanced postsynaptic ion conductance in HA.
  4. Potential Application Value: The findings may offer new targets for developing interventions against heat stress and anxiety.

Other Valuable Information

The study also noted that BDNF levels in human serum increase after heat exposure, suggesting a potential conservation of HA mechanisms between mice and humans. This finding provides a possibility for translating the research results to humans.

Through this study, we have not only gained a deeper understanding of the neural mechanisms of HA but also laid an important foundation for future research on heat stress management and exercise optimization.