• Modeling Mechanism：

  Penitrem A (PA), as a potent tremorogen, induces neurological abnormalities through core mechanisms: ① It selectively antagonizes calcium-dependent potassium-BK (Maxi-K) channels in the central nervous system (CNS), inhibiting potassium ion efflux and leading to abnormally increased neuronal excitability; ② It disrupts neurotransmitter balance, upregulating levels of glutamate (GLU), aspartate (ASP), γ-aminobutyric acid (GABA), dopamine (DA), and serotonin (5-HT), while downregulating norepinephrine (NE), causing signal transduction disorders; ③ It induces oxidative stress (increased NO and MDA, decreased TAC), leading to cerebellar Purkinje cell necrosis, cerebral neuronal apoptosis, and focal hemorrhage, mimicking the core pathological features of tremor-related neurological diseases.

• Related Products：

  Penitrem A (T12403)

• Modeling Method：

  Experimental Subject：

  Caenorhabditis elegans, N2 wild-type, L1 larval stage
  Rat, Sprague Dawley, 3 months old, 100–120 g

  Dosage and Administration Route：

  ① Core modelling:
  - Nematodes: PA (1–2 μM) added to Nematode Growth Medium (NGM), incubated for 42 hours;
  - Rats: PA (46.5 mg/kg feed) mixed into standard diet, administered orally for 4 consecutive weeks;
  ② Control treatment: sham group (rats fed standard diet only, nematodes cultured in NGM medium only);
  ③ Intervention validation (optional):
  - Astaxanthin (AST): Rats 12 mg/kg, dissolved in corn oil, oral gavage;
  - Docosahexaenoic acid (DHA): Rats 250 mg/kg, dissolved in corn oil, oral gavage;
  - Administration timing: synchronised with PA modelling.

  Dosing Frequency and Duration Model：

  Continuous feeding for 4 weeks

• Validation：

  Behavioral indicators: 1. Nematodes: PA (2 μM) treatment significantly increased the number of reverse movements (p<0.05), and AST/DHA intervention could reverse this abnormality; 2. Rats: Spontaneous tremor appeared after 4 weeks of PA feeding, and AST/DHA could alleviate the tremor symptoms; Molecular indicators: Rat brain homogenates: GLU, ASP, GABA, DA, and 5-HT were significantly increased (p<0.05), and NE was significantly decreased (p<0.05); serum/brain NO and MDA were increased (p<0.05), and TAC was decreased (p<0.05); Histological indicators: Purkinje cell necrosis, molecular layer vacuolation, neuronal necrosis, and focal hemorrhage in rat cerebellum (HE staining verification) were observed, and AST/DHA intervention could significantly improve pathological damage.

*Precautions： After blood samples were collected, the animal was euthanized via cervical dislocation.

*References：Goda AA,et,al. Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A. Mar Drugs. 2016 Nov 9;14(11):208.