• Modeling Mechanism：

  Lactacystin, as an irreversible proteasome inhibitor, induces PD pathology through multiple mechanisms: ① It inhibits the function of the ubiquitin-proteasome system, leading to the aggregation of abnormal proteins such as αSyn to form inclusion bodies, mimicking the characteristic Lewy body pathology of PD; ② It induces an imbalance in histone deacetylation (reduced H3-K9 acetylation level), inhibits the expression of neurotrophic factors, and exacerbates the apoptosis of dopaminergic neurons in the substantia nigra pars compacta (SNpc); ③ It damages the substantia nigra-striatum pathway, leading to motor dysfunction, while also causing neuroanatomical changes such as midbrain shrinkage and lateral ventricle dilation.

• Related Products：

  Lactacystin (T15702)

• Modeling Method：

  Experimental Subject：

  Rats: Sprague Dawley (SD) strain, male, body weight 250±10g

  Dosage and Administration Route：

  ① Core modelling: Lactacystin (10 μg/4 μL), dissolved in 0.9% saline (concentration 2.5 μg/μL), unilateral stereotaxic injection into substantia nigra pars compacta (SNpc) (coordinates: bregma posterior - 5.2 mm, lateral+2.5 mm, subdural - 7.6 mm), Injection rate 1 μL/min, needle retention for 3 minutes;
  ② Surgical procedure: Isoflurane inhalation anaesthesia, local scalp injection of bupivacaine for anaesthesia, postoperative administration of buprenorphine for analgesia and glucose-saline solution for fluid replacement;
  ③ Control treatment: Isovolumetric saline solution administered via identical injection protocol;
  ④ Intervention validation (optional): Sodium valproate (200/400 mg/kg), Intraperitoneal injection, Initiated 7 days post-modelling, continued for 28 days

  Dosing Frequency and Duration Model：

  Single-dose Lactacystin injection

• Validation：

  Behavioral indicators: Motor function: One week after modeling, the proportion of contralateral forelimb use decreased, reaching only about 35% in the saline group at five weeks; amphetamine-induced rotational behavior increased (cumulative rotation count significantly increased at five weeks), and sodium valproate intervention could reverse the effect in a dose-dependent manner; Imaging indicators: MRI showed a significant reduction in midbrain volume (ipsilateral side) one week after modeling, with enlarged lateral ventricle volume, and tensor morphometry (TBM) confirmed atrophy of the cortex (cingulate gyrus, motor cortex) and basal ganglia; Pathological indicators: SNpc tyrosine hydroxylase (TH) positive neurons decreased by 64.24±11.34% at five weeks, and Nissl staining confirmed neuronal death (loss of non-TH enzyme expression); Molecular indicators: Decreased H3-K9 acetylation level in brain tissue, downregulated expression of neurotrophic factors (BDNF, GDNF) and anti-apoptotic factor Bcl2, and αSyn aggregation forming inclusion bodies.

*Precautions： Rats were housed in an environment of 21±1℃ and 55±10% humidity, with a 12-hour light-dark cycle.

*References：Harrison IF,et,al. Neurorestoration induced by the HDAC inhibitor sodium valproate in the lactacystin model of Parkinson's is associated with histone acetylation and up-regulation of neurotrophic factors. Br J Pharmacol. 2015 Aug;172(16):4200-15.