QRFP Neuron Stimulation for Inducing Reversible Hibernation

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Solution Overview

Problem

Current methods lack the ability to artificially induce a hibernation-like state in non-hibernating animals, including humans, which is essential for various applications such as long-range space exploration and understanding the neural mechanisms of hibernation and daily torpor.

Innovation Solution

Applying an excitatory stimulus to pyroglutamylated RFamide peptide (QRFP)-producing neurons in the anteroventral periventricular nucleus (AVPe), medial preoptic area (MPA), and periventricular nucleus (Pe) regions of the hypothalamus, using devices that either electrically or chemically stimulate these neurons, to induce a hibernation-like state characterized by reduced metabolic and thermal set-points.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Use of energy by moving object

If excitatory manipulation of QRFP-producing neurons is applied, then metabolic rate decreases significantly, but the mechanism remains unclear and cannot be controlled precisely

Engineering Contradiction:

Improvemetabolic rateVSAvoidneural mechanism control

Core Design Contradiction:

Use of energy by moving objectVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies selective stimulation to QRFP-producing neurons located in specific hypothalamic regions (AVPe, MPA, Pe) rather than diffuse stimulation. This localized approach enables precise control of the neural mechanism while achieving significant metabolic reduction, resolving the contradiction between energy reduction and control precision.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent introduces a controllable stimulation device as an intermediary to manipulate QRFP-producing neurons. This device serves as a mediator between external control and the neural system, enabling precise regulation of metabolic rate through electrical or chemical stimulation while maintaining clear control over the mechanism.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Loss of energy

If body temperature is reduced to achieve hibernation-like state, then energy consumption decreases, but the animal loses responsiveness to environmental changes

Engineering Contradiction:

Improveenergy consumptionVSAvoidresponsiveness to environmental changes

Core Design Contradiction:

Loss of energyVSAdaptability or versatility

Solution Approach 1:

The patent implements dynamic control of the hibernation-like state through adjustable stimulation parameters. The stimulation intensity and duration can be modified to achieve different levels of metabolic reduction and temperature lowering, allowing the system to adapt dynamically between energy conservation mode and responsiveness mode, thus resolving the contradiction between energy loss and adaptability.

Inventive Principle:

Principle #15Dynamics

3Duration of action of moving object

If artificial hibernation-like state is induced, then long-range space exploration becomes feasible, but current methods lack reversibility and tissue damage

Engineering Contradiction:

Improveduration of hibernation-like stateVSAvoidreversibility without tissue damage

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent incorporates feedback mechanisms to monitor the state of the animal during stimulation. By continuously monitoring physiological parameters and adjusting stimulation intensity accordingly, the system ensures reversible induction of hibernation-like state without exceeding safe thresholds that could cause tissue damage. This feedback control enables long-duration application while maintaining reliability and safety.

Inventive Principle:

Principle #23Feedback

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach effectively induces a hibernation-like state with significant reductions in metabolic rate and body temperature, allowing for energy conservation while maintaining responsiveness to environmental changes, and is reversible without tissue damage.

Implementation Method 1

a voltage generator that receives the control signal from the controller and generates a voltage; a stimulation probe that is electrically connected proximally to the voltage generator and includes an electrical stimulation electrode at a distal end, the stimulation prove having sufficient length for accessing QRFP-producing neurons from a brain surface, and generating an electrical stimulus at the electrical stimulation electrode at the distal end through the voltage from the voltage generator

Methodology Applied

Scientific EffectElectrical stimulation: Electric Field

Implementation Method 2

applying, in the brain of the subjects, an excitatory stimulus to pyroglutamylated RFamide peptide (QRFP) gene-expressing neurons in regions of the hypothalamus including the anteroventral periventricular nucleus (AVPe), the medial preoptic area (MPA) and the periventricular nucleus (Pe)... the metabolic rate decreases to one-third or less, but unlike an anesthetized state, the mice still react to changes in ambient temperature

Methodology Applied

Scientific EffectMetabolic reduction:

Data Source

PatentUS20220323761A1Method for inducing hibernation-like state and device same

Publication Date: 2022.10.13 RIKEN CO LTD

AI summary

A method for inducing a hibernation-like state and a device for the same is described. The method is a chemical and physical method for reducing, in a subject, a theoretical set-point temperature of a body temperature and/or a feedback gain of heat production, or for inducing a hibernation-like state in the subject, the method including applying an excitatory stimulus to pyroglutamylated RFamide peptide (QRFP)-producing neurons. A device used to implement the method is also described.